Medic Alert Bracelets

Posted on December 16, 2025 by MaryO

Since the last topic was about Adrenal Insufficiency, it seemed that a great next topic would be about Medic Alert Bracelets.

Many doctors insist that everyone who has had pituitary or adrenal surgery have a bracelet – and some will even tell patients what they should say on them.

While I was still a patient at the NIH (National Institutes of Health) after my pituitary surgery, I was given my first bracelet along with my kit in care of adrenal crisis.  I had to learn to give myself a shot before I could go home.

Now, my endo checks mine at every visit to be sure I’m wearing my bracelet and reads it to be sure it’s still legible and checks to see what the text says.

He feels that the bracelets – and he insists that they LOOK like medic alert bracelets, not disguised as jewelry – are life savers.

I’m not so sure – I read stories on the message boards that people have gone into AI (adrenal insufficiency and no one has ever looked at their bracelet.  That was certainly the case for young Sam.  Her mom had instructions everywhere, none were heeded and the situation rapidly turned disastrous.

…We have dealt with Addison’s for 7 years; but I have handled everything. Apparently the vials of solu-cortef with step-by-step instructions hanging on the bulletin board in the kitchen, medicine cabinet and in every vehicle somehow missed his attention…  (read the whole story at survive the journey: Stars Go Blue)

A Paramedic wrote on the message boards:

I’d like to add a couple things from the perspective of a Paramedic…

A lot of us are not taught about adrenal insufficiency during our education….nor do many of us (if any at all) have a protocol to administer Injectable for AI unless we are able to contact the ER doctor for permission. So…if any of you should have an AI crisis please gently nudge your paramedic to contact the receiving physician for permission to administer the medication. I know this sounds like a lot of responsibility on the part of the patient…but you have to realize that we’re taught to recognize the most common life threats and endocrine disorders (other than diabetes) most usually do not present with life threats (we all know that as cushing’s is more recognized that this will change)…and our protocols cover the most common life threats….so while we may recognize that you are hypotensive and need fluids (IV) and are sweaty, nauseated, decreased level of responsiveness etc…we are not equipped to deal with the actual cause unless you help educate us….

Also…please don’t get angry with us….if we are having problems understanding…just gently insist that a call be made to your doctor or the receiving ED (usually not feasible for us to call your doctor since they do not come to the phone for just anybody but if you have access to them, as many cushies do, it would be great to talk to them)…

Paramedicine is evolving….someday soon, hopefully, our education will include more diagnostic skills…untill just in the past 5 years or so we were NEVER to make a diagnosis at all…just treat the symptoms!!!! So there is hope out there for futher understanding of such a critical problem for those without adrenal (or asleep adrenals) glands….

The medical alert jewerly is a life-saver and we do look for it….

So, the questions for discussion are:

  • Do you have a medical alert bracelet
  • Does your doctor check on it or suggest proper wording.
  • If you have one, has any medical staff read it during a crisis
  • And… what does yours say?

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Three Cases of Ectopic, Cyclic Cushing Syndrome: A New Square Wave Variant

Posted on November 3, 2025 by MaryO

Abstract

Cyclic Cushing syndrome (CCS) is characterized by unpredictable, intermittent phases of excess cortisol, alternating with periods of normal or subnormal adrenocorticotropic hormone (ACTH) and cortisol levels. The mechanism is unclear. Due to its rarity and diverse clinical presentation, unpredictable phases, and various etiologies, CCS poses significant diagnostic and management challenges for endocrinologists. The authors describe 3 cases in which each patient’s initial presentation was a life-threatening hypercortisolemic phase that lasted from 4 days to 3 months, followed by spontaneous resolution to prolonged eucortisolemic phases lasting from 10 to 26 months. Further testing indicated an ectopic ACTH-secreting source; however, the locations of the offending tumors were indeterminate. The authors propose the term square wave CCS variant to characterize the unique, prolonged intercyclic phases of hypercortisolemia and eucortisolemia with this subtype that are distinct from conventional CCS characterized by shorter phases of transient hypercortisolemia shifting to periods of eucortisolemia or hypocortisolemia. This uncharacteristic pattern of cyclicity poses diagnostic and therapeutic challenges, thus underscoring the importance of careful diagnostic workup and treatment of these patients.

Keywords: ectopic, cyclic, Cushing syndrome, eucortisolemia, hypercortisolemia

Introduction

Cyclic Cushing syndrome (CCS) is a rare variant of Cushing syndrome (CS) characterized by intermittent episodes of cortisol peaks alternating with variable periods of normal or subnormal adrenocorticotropic hormone (ACTH) and cortisol levels (troughs) []. These cycles can occur at regular or irregular intervals [], with unpredictable intercyclic phases typically lasting from days to months [, ]. The prevalence of CCS in patients with CS is low, ranging from 8% to 19% []. Several alternative terms (eg, intermittent, variable, periodic, and episodic hypercortisolism) have been proposed to characterize the variable cyclicity of ACTH and cortisol secretion in patients with CCS [].

We describe 3 cases of suspected ectopic ACTH-dependent CS with an indeterminate ACTH source that presented with life-threatening hypercortisolemia lasting from 4 days to 3 months, followed by spontaneous eucortisolemic phases lasting from 10 to 26 months. The term square wave is proposed to describe this unique cyclic pattern to highlight the unpredictability of severe hypercortisolemia followed by spontaneous prolonged eucortisolemic phases, which is distinct from previously described transient regular or irregular cycles with shorter intercyclic phases of CCS that require medical intervention.

Case Presentation

Case 1

A 75-year-old man with atrial fibrillation, bilateral leg edema, 6-month weight loss of 7 pounds (3.2 kg), and generalized muscle weakness was referred for cardiac ablation therapy. However, just before he underwent the procedure, he was found to be profoundly hypokalemic with potassium of 2.9 mEq/L (SI: 2.9 mmol/L) (reference range, 3.6-5.3 mEq/L [SI: 3.6-5.3 mmol/L]) and hyperglycemic, with blood glucose of 498 mg/dL (SI: 27.8 mmol/L) (reference range, 70-99 mg/dL [SI: 3.9-5.5 mmol/L]) and glycated hemoglobin (HbA1c) of 7.4%. He was emergently treated with potassium supplementation and insulin therapy.

Case 2

A 61-year-old woman presented to the emergency department with palpitations, uncontrolled hypertension, weight loss of 20 pounds (9.1 kg) over 2 weeks, new signs of hyperandrogenism (eg, hirsutism, acne, muscle atrophy), lower back pains, easy bruising, and proximal muscle weakness.

Case 3

A 57-year-old woman presented to the emergency department in August 2021 with a 2-month history of facial swelling and generalized muscle weakness. She had reported a similar episode in April 2019 with hypokalemia (potassium, 2.5 mEq/L [SI: 2.5 mmol/L]) that was treated with potassium repletion therapy.

Diagnostic Assessment

Case 1

Further laboratory tests revealed elevated morning (Am) cortisol of 76.8 µg/dL (SI: 2119 nmol/L) (reference range, 5-25 µg/dL [SI: 138-690 nmol/L]), Am ACTH of 368 pg/mL (SI: 81 pmol/L) (reference range, 6-50 pg/mL [SI: 1.3-11.0 pmol/L]), and 24-hour urine free cortisol (UFC) of 4223 µg/24 hours (SI: 11 656 nmol/24 hours) (reference range, 1.5-18.1 µg/24 hours [SI: 4-50 nmol/24 hours]) (Table 1). Magnetic resonance imaging (MRI) of the pituitary (Fig. 1) and 68Ga-DOTATATE positron emission tomography (PET) (Table 2) of the chest, pelvis, and abdomen failed to identify the source of ACTH secretion. Inferior petrosal sinus sampling (IPSS) showed no significant ACTH gradient, supporting the likelihood of an ectopic ACTH-secreting source (Table 3).

Table 1.

Summary of biochemical testing data for the 3 patients with a square wave pattern of cyclic Cushing syndrome

Test, reference range Patient 1 (male, 75 years) Patient 2 (female, 61 years) Patient 3 (female, 57 years)
IP EP IP EP IP EP
AM cortisol 5-23 µg/dL (138-690 nmol/L) 76.8 µg/dL (2119 nmol/L) 14.2 µg/dL (392 nmol/L) 38.4 µg/dL (1060 nmol/L) 17.9 µg/dL (494 nmol/L) 56.8 µg/dL (1568 nmol/L) 14.4 µg/dL (397 nmol/L)
AM ACTH 6-50 pg/mL (1.3-11.0 pmol/L) 368 pg/mL (81 pmol/L) 38.1 pg/mL (8.4 pmol/L) 118 pg/mL (26 pmol/L] 16.5 pg/mL (3.6 pmol/L) 159 pg/mL (35 pmol/L] 39 pg/mL (8.6 pmol/L)
PM cortisol 2.9-17.3 µg/dL (80-477 nmol/L) 57.8 µg/dL (1594 nmol/L) — — — — <0.05 µg/dL (<1.4 nmol/L)
24-h UFC 1.5-18.1 µg/24 hours (4-50 nmol/24 hours) 4223 µg/24 hours (11 656 nmol/24 hours) 10.5 µg/24 hours (29 nmol/24 hours) 52.9 µg/24 hours (146 nmol/24 hours) 13 µg/24 hours (36 nmol/24 hours) 670.5 µg/24 hours (1851 nmol/24 hours) 23 µg/24 hours (63 nmol/24 hours)
Post 1-mg DST cortisol <1.8 ng/dL (<50 nmol/L) 74.6 ng/dL (2059 nmol/L) — 26.9 ng/dL (743 nmol/L) 1.4 ng/dL (<50 nmol/L) 16.7 ng/dL (461 nmol/L) —
Salivary cortisol < 0.09 µg/dL (<2.5 nmol/L) — 0.08 µg/dL (2.2 nmol/L) — 0.04 µg/dL (1.1 nmol/L) — —
S-DHEA 7-162 µg/dL (0.19-4.37 µmol/L) — 63 µg/dL — — — —
Chromogranin A <311 ng/mL* (<311 µg/L) 725 ng/mL (30.6 nmol/L) — — — — —
Lipase 8-78 U/L 40.0 U/L (40.0 U/L) — — — — —
Hemoglobin A1c <5.7% 8.9% 5.9% 9.2% 5.9% — —

International System of Units are included within parentheses.

Dash (–) indicates that no data are available.

* Method dependent.

Abbreviations: ACTH, adrenocorticotropic hormone; AM, morning; DST, dexamethasone suppression test; EP, eucortisolemic phase; IP, initial presentation; PM, afternoon; S-DHEA, serum dehydroepiandrosterone; UFC, urine free cortisol.

Figure 1.

Figure 1.

Case 1. (A) Sagittal and (B) coronal magnetic resonance images demonstrating normal appearance of the pituitary gland. From Barrow Neurological Institute, Phoenix, Arizona.

Table 2.

Imaging workup summary

Case Imaging modalities Interpretation
Case 1 Pituitary MRI, CT chest/abdomen/pelvis, pelvic USG, 68Ga-DOTATATE PET/CT No ectopic ACTH-secreting source identified
Case 2 Pituitary MRI, CT chest/abdomen/pelvis, 68Ga-DOTATATE PET/CT No ectopic ACTH-secreting source identified
Case 3 Pituitary MRI, CT chest/abdomen/pelvis, pelvic USG, 68Ga-DOTATATE PET/CT No ectopic ACTH-secreting source identified

Abbreviations: ACTH, adrenocorticotropic hormone; CT, computed tomography; MRI, magnetic resonance imaging; PET, positron emission tomography; USG, ultrasound.

Table 3.

ACTH levels from inferior petrosal sinus sampling

Variable −5 Minutes 0 Minutes +2 Minutes +5 Minutes +10 Minutes
CASE 1
Right IPS 239 pg/mL (52.6 pmol/L) 221 pg/mL (48.6 pmol/L) 218 pg/mL (48.0 pmol/L) 239 pg/mL (52.6 pmol/L) 217 pg/mL (47.8 pmol/L)
Left IPS 226 pg/mL (49.8 pmol/L) 221 pg/mL (48.6 pmol/L) 216 pg/mL (47.6 pmol/L) 251 pg/mL (55.3 pmol/L) 213 pg/mL (46.9 pmol/L)
Peripheral 225 pg/mL (49.5 pmol/L) 219 pg/mL (48.2 pmol/L) 210 pg/mL (46.2 pmol/L) 217 pg/mL (47.8 pmol/L) 237 pg/mL (52.2 pmol/L)
Right IPS: peripheral ratio 1.06 1.00 1.03 1.10 .92
Left IPS: peripheral ratio 1.00 1.00 1.02 1.15 .89
CASE 2
Right IPS 59 pg/mL (13.0 pmol/L) 79 pg/mL (17.4 pmol/L) 203 pg/mL (44.7 pmol/L) 296 pg/mL (65.2 pmol/L) 374 pg/mL (82.3 pmol/L)
Left IPS 61 pg/mL (13.4 pmol/L) 77 pg/mL (17.0 pmol/L) 196 pg/mL (43.2 pmol/L) 313 pg/mL (68.9 pmol/L) 341 pg/mL (75.1 pmol/L)
Peripheral 62 pg/mL (13.7 pmol/L) 64 pg/mL (14.1 pmol/L) 146 pg/mL (32.2 pmol/L) 235 pg/mL (51.8 pmol/L) 368 pg/mL (81.0 pmol/L)
Right IPS: peripheral ratio .95 1.23 1.39 1.26 1.02
Left IPS: peripheral ratio .98 1.20 1.34 1.33 .93
CASE 3
Right IPS 119 pg/mL (26.1 pmol/L) 121 pg/mL (26.6 pmol/L) 380 pg/mL (83.8 pmol/L) 581 pg/mL (128.0 pmol/L) 232 pg/mL (51.2 pmol/L)
Left IPS 124 pg/mL (27.4 pmol/L) 133 pg/mL (29.3 pmol/L) 358 pg/mL (78.9 pmol/L) 568 pg/mL (125.0 pmol/L) 262 pg/mL (57.7 pmol/L)
Peripheral 113 pg/mL (24.9 pmol/L) 111 pg/mL (24.4 pmol/L) 322 pg/mL (70.9 pmol/L) 527 pg/mL (116.0 pmol/L) 178 pg/mL (39.1 pmol/L)
Right IPS: peripheral ratio 1.04 1.09 1.18 1.10 1.31
Left IPS: peripheral ratio 1.10 1.20 1.13 1.08 1.48

International System of Units are included within parentheses.

Baseline IPS: P > 2.0; Suggests pituitary (Cushing’s disease).

Post-stim IPS: P > 3.0; Confirms pituitary ACTH source.

Abbreviations: ACTH, adrenocorticotropic hormone; IPS, inferior petrosal sinus.

Case 2

Laboratory tests revealed elevated Am cortisol of 38.4 µg/dL (SI: 1060 nmol/L) and Am ACTH of 118 pg/mL (SI: 26 pmol/L), hypokalemia (potassium, 2.9 mEq/L [SI: 2.9 mmol/L]) and new-onset type 2 diabetes mellitus with a random blood glucose of 489 mg/dL (SI: 27.2 mmol/L) and HbA1c of 9.2% (reference range, < 5.7%) (Table 1). Lumbar spine radiography and spine MRI demonstrated compression fractures of L1 to L4 vertebrae, and pituitary MRI showed a 2-mm hypo-enhancing foci within the midline and to the right of the pituitary gland (Fig. 2).

Figure 2.

Figure 2.

Case 2. (A) Sagittal and (B) coronal magnetic resonance images of the pituitary gland show 2-mm hypo-enhancing foci (arrows) within the midline and to the right side of the pituitary gland. From Barrow Neurological Institute, Phoenix, Arizona.

Case 3

During the present hospital admission, the patient was hypokalemic (potassium, 2.7 mEq/L [SI: 2.7 mmol/L]) and hypercortisolemic with Am cortisol and Am ACTH levels of 56.8 µg/dL (SI: 1568 nmol/L) and 159 pg/mL (SI: 35 pmol/L), respectively. After 4 days of hospitalization, the patient spontaneously became eucortisolemic with an Am cortisol of 16.8 µg/dL (SI: 464 nmol/L), 24-hour UFC of 670.5 µg/24 hours (SI: 1851 nmol), and late-night salivary cortisol of 0.03 µg/dL (SI: 0.828 nmol/L) with symptom improvement (Table 1). Pituitary MRI revealed a flattened, normal-appearing pituitary gland (Fig. 3).

Figure 3.

Figure 3.

Case 3. (A) Sagittal and (B) coronal magnetic resonance images of the pituitary gland showing a flattened pituitary gland. No discrete, sizable, differentially enhancing mass is detected within the sella. From Barrow Neurological Institute, Phoenix, Arizona.

Treatment

Case 1

Because of the patient’s worsening clinical condition and severe hypercortisolemia with no identifiable ACTH source, ketoconazole was considered to induce eucortisolemia. While electrocardiography and liver function tests were being measured before starting ketoconazole, the patient’s Am cortisol levels spontaneously normalized to 14.2 µg/dL (SI: 392 nmol/L) with symptomatic improvement.

Case 2

The patient began insulin, spironolactone, and levothyroxine therapy. After 2 days in the hospital, her Am cortisol decreased to 17.9 µg/dL (SI: 494 nmol/L) and remained within the range of 9.4 to 17.9 µg/dL (SI: 259-494 nmol/L). An IPSS performed 3 weeks later showed no significant ACTH gradient, supporting the likelihood of an ectopic ACTH-secreting source. By month 3, her Am cortisol levels consistently remained below 15 µg/dL (SI: 414 nmol/L). Blood pressure was controlled with one antihypertensive agent, and insulin was discontinued due to frequent hypoglycemic episodes.

Case 3

The patient was readmitted 18 months later with worsening muscle weakness, uncontrolled hypertension, hypokalemia (potassium, 2.4 mEq/L [SI: 2.4 mmol/L]), and hypercortisolemia with elevated Am cortisol and Am ACTH levels. 68Ga-DOTATATE PET did not reveal an ectopic ACTH source (Table 2), and IPSS did not reveal any significant ACTH gradient (Table 3). However, computed tomography (CT) of the chest, abdomen, and pelvis revealed a 0.7-cm lung nodule. During this hospitalization, the patient received supportive treatment, including antihypertensive therapy and electrolyte replacement. No pharmacologic intervention was required to control her cortisol levels.

Outcome and Follow-Up

Case 1

Late-night salivary cortisol levels measured were within the normal range (0.08 µg/dL, 0.06 µg/dL, and 0.08 µg/dL [SI: 2.2 nmol/L, 1.7 nmol/L, and 2.2 nmol/L]; reference range, < 0.09 µg/dL [SI: < 2.5 nmol/L]). Because of these biochemical and symptomatic improvements, ketoconazole therapy was deferred. At the most recent outpatient clinic follow-up 26 months after his cortisol levels normalized, the patient remained in remission without recurrence of hypercortisolemic symptoms.

Case 2

The patient remained in biochemical and clinical remission for 15 months until she began experiencing abdominal distention, bilateral leg edema, and facial swelling again. Blood pressure increased at this time, requiring 3 antihypertensive medications. Her Am cortisol levels rose to 29.1 µg/dL (SI: 803 nmol/L), but repeat IPSS showed no ACTH gradient, and 68Ga-DOTATATE PET/CT of the chest, abdomen, and pelvis was unremarkable (Tables 2 and 3). Block-and-replace therapy of osilodrostat and hydrocortisone was initiated to preemptively prevent hypercortisolemic episodes; after 3 months of therapy, she underwent successful bilateral adrenalectomy (BLA).

Case 3

On day 5 of hospitalization, her Am cortisol level decreased to 14.4 µg/dL (SI: 397 nmol/L) (reference range, 5-25 µg/dL [SI: 138-690 nmol/L]). Her symptoms improved, and she remained well for 11 months before recurrence of muscle weakness, hypokalemia, and hypercortisolemia with an Am cortisol of 58.7 µg/dL (SI: 1620 nmol/L) and Am ACTH of 194 pg/mL (SI: 43 pmol/L). The patient became eucortisolemic without any medical intervention and declined further treatment. She continues with regular outpatient follow-up.

Discussion

Diagnosing CCS poses considerable challenges because of its heterogeneous clinical manifestations, erratic intercyclic duration, frequency of phases, and various etiologies. Patients may experience transient or continuous symptoms with variable degrees of severity []. Our patients presented with severe hypercortisolemia lasting from days to months, followed by an extended period of spontaneous eucortisolemia, lasting from months to years. This unique presentation of cortisol kinetics differs from the classic presentation of CCS, which typically features shorter intercyclic phases [].

We coined the term square wave variant of CCS to characterize this unique feature of prolonged cyclicity of hypercortisolemia shifting spontaneously to eucortisolemia without medical intervention. The term square wave was chosen because the cortisol secretion pattern in these cases resembles a square waveform, with abrupt transitions between prolonged periods of high and low cortisol levels rather than the gradual fluctuations or short irregular peaks seen in typical CCS. This visual and kinetic analogy helps distinguish the pattern observed in our patients from the more classically described forms of CCS.

The absence of a standardized definition of CCS complicates the classification of cases such as ours, which diverge from conventional descriptions in the medical literature [, , ]. Most cases of CCS are associated with pituitary tumors (67%), whereas ectopic ACTH-secreting tumors (17%) and adrenal tumors (11%) are less common [, ]. Our patients had evidence of ectopic CS, of which the ACTH-secreting source was unidentifiable despite extensive imaging. The variability of symptom duration, severity, and timing in our patients implies distinct mechanisms for suppressing or desensitizing adrenal cortisol synthesis during the extended symptom-free periods. Other mechanisms include enhanced effects of specific neurotransmitters, hypothalamic dysregulation, spontaneous tumor hemorrhage, cyclic growth and apoptosis of ACTH-secreting tumor cells, and positive and negative feedback mechanisms []. Another explanation for the prolonged eucortisolemic phase may be due to altered POMC gene expression and defective ACTH secretion from the ectopic tumor []. Over time, the tumor may dedifferentiate or develop a transcriptional or posttranscriptional defect, leading to the secretion of ACTH with a decreased ability to stimulate adrenal cortisol secretion [, ]. Conversely, CCS might also be an exaggerated physiological cyclical variation of ACTH and cortisol secretion [, ]. However, the prolonged eucortisolemic phase observed in our patients argues against this exaggeration theory.

Recent studies have suggested that the anomalous cyclicity of cortisol and ACTH may be influenced by dysregulation of the peripheral clock system in endocrine tumors []. Certain tumors may exhibit aberrant expression of circadian regulators such as CLOCK, PER1, PER2, PER3, and TIMELESS, which can disrupt the physiological rhythmicity of cortisol and ACTH secretion [, ]. For instance, cortisol-secreting adrenal adenomas demonstrate downregulation of PER1, CRY1, and Rev-ERB, whereas adrenocortical carcinomas upregulate CRY1 and PER1 and downregulate BMAL1 and RORα. In patients with CS, clock gene expression in peripheral blood mononuclear cells has been shown to be significantly flattened, contributing to the loss of circadian variation in cortisol levels [].

Surgery is the preferred treatment option for CCS patients, provided the tumor is localizable []. Medical therapy is used when the tumor is undetectable, unresectable, or recurs. Medical therapy can overtreat and induce iatrogenic adrenal insufficiency during the eucortisolemic phases. This risk can be mitigated by the block-and-replace strategy of high-dose steroidogenesis inhibitors to suppress adrenal cortisol production and supplemented with exogenous glucocorticoids []. In patients for whom the ectopic tumor is unidentifiable, the initial tumor resection is ineffective, or if medical management does not adequately control hypercortisolemia, BLA may be considered [].

Although treatment of CCS resembles that of CS, the heterogeneity in the severity and duration of symptoms prohibits the implementation of some conventional treatment strategies. Consequently, long-term medical therapy may not align with the patient’s preferences, especially those whose course of illness is characterized by prolonged eucortisolemia and milder symptoms. Such patients should be educated to monitor symptoms closely during the eucortisolemic phase to recognize the signs and symptoms of hypercortisolism using objective parameters such as self-assessment of weight, blood pressure, and capillary blood glucose. Periodic biochemical monitoring may also be helpful, including standby kits for self-testing of late-night salivary cortisol and 24-hour UFC. If the source of ectopic ACTH secretion continues to elude detection, BLA during the eucortisolemic phase may be considered to prevent future life-threatening hypercortisolemic episodes.

Learning Points

  • Unlike typical CCS, there may be a subset of patients with a distinct square wave variant of CCS marked by severe hypercortisolemia followed by prolonged periods of eucortisolemia.
  • Ectopic ACTH-secreting sources in CCS may be linked to unusually long symptom-free intervals of eucortisolemia and hypocortisolemia between episodes of hypercortisolemia.
  • If possible, CCS management should be individualized to address its cause, with vigilant monitoring during the eucortisolemic phase to detect potential recurrence early.
  • If the source of the ectopic ACTH-secreting tumor is not identifiable, BLA may be considered during the eucortisolemic phase to prevent future life-threatening hypercortisolemic episodes.

Acknowledgments

We thank the staff of Neuroscience Publications at Barrow Neurological Institute for assistance with manuscript preparation.

Abbreviations

ACTH
adrenocorticotropic hormone
BLA
bilateral adrenalectomy
CCS
cyclic Cushing syndrome
CS
Cushing syndrome
CT
computed tomography
HbA1c
glycated hemoglobin
IPSS
inferior petrosal sinus sampling
MRI
magnetic resonance imaging
PET
positron emission tomography
UFC
urine free cortisol

Contributor Information

Mercedes Martinez-Gil, Department of Internal Medicine, Creighton University School of Medicine, Phoenix, AZ 85012, USA.

Tshibambe N Tshimbombu, Department of Neurology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ 85013, USA.

Yvette Li Yi Ang, Division of Endocrinology, Department of Medicine, National University Hospital, Singapore 119228, Singapore.

Monica C Rodriguez, Barrow Pituitary Center, Barrow Neurological Institute, University of Arizona College of Medicine and Creighton University School of Medicine, Phoenix, AZ 85012, USA.

Kevin C J Yuen, Barrow Pituitary Center, Barrow Neurological Institute, University of Arizona College of Medicine and Creighton University School of Medicine, Phoenix, AZ 85012, USA.

Contributors

All authors contributed substantially to the manuscript. K.C.J.Y. supervised the project, provided content review, and edited the text. M.M.-G. and T.N.T. contributed equally to the preparation, writing, and submission of the manuscript. M.C.R. was responsible for the clinical management of one of the cases. Y.L.Y.A. contributed to the diagnosis, management, and writing of one of the cases. All authors reviewed and approved the final version of the manuscript.

Funding

All authors declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this manuscript.

Disclosures

The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this manuscript.

Informed Patient Consent for Publication

Signed informed consents were obtained directly from the patients.

Data Availability Statement

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

https://pmc.ncbi.nlm.nih.gov/articles/PMC12559019/

Filed under: Cushing's, Rare Diseases, symptoms | Tagged: , , , , | Leave a comment »

Day 26, Cushing’s Awareness Challenge

Posted on April 26, 2024 by MaryO

So often during the diagnosis phase of Cushing’s I felt lost like this picture – I was walking alone to an unknown place with an unknown future.

My diagnosis was pre-Internet which meant that any information had to be gotten from libraries, bookstores, magazines…or doctors.  In 1983 to 1986 I knew something was terribly wrong but there was no backup from doctors, family or friends.  My first hope was from a magazine (see Day Six)

After I got that first glimmer of hope, it was off to the library to try to understand medical texts.  I would pick out words I did understand – and it was more words each trip.  I made Xerox copies of my findings to read at home and try to digest. (I still have all those old pages!)

All my research led me to Cushing’s.

Unfortunately, the research didn’t lead me to doctors who could help for several years.  That contributed greatly to the loneliness.  If a doctor says you’re not sick, friends and family are going to believe the doctor, not you.  After all, he’s the one trained to know what’s wrong or find out.

I was so grateful when I finally got into a clinical trial at NIH and was so nice not to be alone with this mystery illness.  I was also surprised to learn, awful as I felt, there were Cushies much worse off than I was.

I am so glad that the Internet is here now helping us all know that we’re not alone anymore.

We’re all in this together with help, support, research, just being there.  I love this quote from Catherine at http://wheniwasyou.wordpress.com/2012/03/31/wheniwasyou/

Mary, I am delighted to see you here. Cushings – because of the persistent central obesity caused by (we know now) the lack of growth hormone plus the hypothyroidism I was diagnosed with (but for which treatment was ineffective due to my lack of cortisol) – was one of the things I considered as an explanation for my symptoms. Your site was enormously educational and helpful to me in figuring out what might be happening to me. Those other patient testimonies I referred to? Many of them were the bios you posted. Thank you so much for commenting. I am so grateful for the support and encouragement. I really hope that my experiences will help other undiagnosed hypopituitary patients find their way to a diagnosis. I often used to dream that one day I’d get to say to others what was so often said to me: don’t give up, there will be an answer. I kept believing in myself because people I hadn’t even met believed in me. Now I am finally here and I do hope my story will help others to have faith in their own instincts.

Thanks again. Please do keep in touch.

Catherine

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Day 13, Cushing’s Awareness Challenge

Posted on April 13, 2024 by MaryO

UVA 2004
Cushing’s Conventions have always been special times for me – we learn a lot, get to meet other Cushies, even get referrals to endos!

As early as 2001 (or before) my pituitary function was dropping.  My former endo tested annually but did nothing to help me with the symptoms.

In the fall of 2002 my endo refused to discuss my fatigue or anything at all with me until I lost 10 pounds. He said I wasn’t worth treating in my overweight condition and that I was setting myself up for a heart attack. He gave me 3 months to lose this weight. Those 3 months included Thanksgiving, Christmas and New Years.  Needless to say, I left his office in tears, again.

Fast forward 2 years to 2004.  I had tried for a while to get my records from this endo. He wouldn’t send them, even at doctors’ or my requests.

I wanted to go see Dr. Vance at UVa but I had no records so she wouldn’t see me until I could get them.

Finally, my husband went to the former endo’s office and threatened him with a court order. The office manager managed to come up with about 13 pages of records. For going to him from 1986 to 2001 including weeks and weeks at NIH and pituitary surgery, that didn’t seem like enough records to me.

In April of 2004, many of us from the message boards went to the UVa Pituitary Days Convention. That’s where the picture above comes in.  Other pictures from that convention are here.

By chance, we met a wonderful woman named Barbara Craven. She sat at our table for lunch on the last day and, after we learned that she was a dietitian who had had Cushing’s, one of us jokingly asked her if she’d do a guest chat for us. I didn’t follow through on this until she emailed me later. In the email, she asked how I was doing. Usually I say “fine” or “ok” but for some reason, I told her exactly how awful I was feeling.

Barbara emailed me back and said I should see a doctor at Johns Hopkins. I said I didn’t think I could get a recommendation to there, so SHE referred me. The doctor got right back to me, set up an appointment. Between his vacation and mine, that first appointment turned out to be Tuesday, Sept 14, 2004.

Just getting through the maze at Johns Hopkins was amazing. They have the whole system down to a science, moving from one place to another to sign in, then go here, then window 6, then… But it was very efficient.

My new doctor was wonderful. Understanding, knowledgeable. He never once said that I was “too fat” or “depressed” or that all this was my own fault. I feel so validated, finally.

He looked through my records, especially at my 2 previous Insulin Tolerance Tests (ITT). From those, he determined that my growth hormone has been low since at least August 2001 and I’ve been adrenal insufficient since at least Fall, 1999 – possibly as much as 17 years! I was amazed to hear all this, and astounded that my former endo not only didn’t tell me any of this, he did nothing. He had known both of these things – they were in the past records that I took with me. Perhaps that was why he had been so reluctant to share copies of those records. He had given me Cortef in the fall of 1999 to take just in case I had “stress” and that was it.

The new endo took a lot of blood (no urine!) for cortisol and thyroid stuff. I went back on Sept. 28, 2004 for arginine, cortrosyn and IGF testing.

He said that I would end up on daily cortisone – a “sprinkling” – and some form of GH, based on the testing the 28th.

For those who are interested, my new endo is Roberto Salvatori, M.D.
Assistant Professor of Medicine at Johns Hopkins

Medical School: Catholic University School of Medicine, Rome, Italy
Residency: Montefiore Medical Center
Fellowship: Cornell University, Johns Hopkins University
Board Certification: Endocrinology and Metabolism, Internal Medicine

Clinical Interests: Neuroendocrinology, pituitary disorders, adrenal disorders

Research Interests: Control of growth hormone secretion, genetic causes of growth hormone deficiency, consequences of growth hormone deficiency.

Although I have this wonderful doctor, a specialist in growth hormone deficiency at Johns Hopkins, in November, 2004, my insurance company saw fit to over-ride his opinions and his test results based on my past pharmaceutical history! Hello??? How could I have a history of taking GH when I’ve never taken it before?

Of course, I found out late on a Friday afternoon. By then it was too late to call my case worker at the drug company, so we had to appeal on Monday. My local insurance person also worked on an appeal, but the whole thing was  just another long ordeal of finding paperwork, calling people, FedExing stuff, too much work when I just wanted to start feeling better by Thanksgiving.

As it turned out the insurance company rejected the brand of hGH that was prescribed for me. They gave me the ok for a growth hormone was just FDA-approved for adults on 11/4/04. The day this medication was approved for adults was the day after my insurance said that’s what is preferred for me. In the past, this form of hGH was only approved for children with height issues. Was I going to be a ginuea pig again?

The new GH company assigned a rep for me, submitted info to pharmacy, and waited for insurance approval, again.

I finally started the Growth Hormone December 7, 2004.

Was the hassle and 3 year wait worth it?

Stay tuned for April 15, 2016 when all will be revealed.

Read

Read Dr. Barbara Craven’s Guest Chat, October 27, 2004

Thanks for reading 🙂

MaryO

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Day 12, Cushing’s Awareness Challenge

Posted on April 12, 2024 by MaryO

In March of 1987, after the endo finally  confirmed that I had Cushing’s, I was sent to a local hospital where they repeated all those same tests for another week and decided that it was not my adrenal gland (Cushing’s Syndrome) creating the problem. The doctors and nurses had no idea what to do with me, so they put me on the brain cancer ward.

When I left this hospital after a week, we didn’t know any more than we had before.

As luck would have it, NIH (National Institutes of Health, Bethesda, Maryland) was doing a clinical trial of Cushing’s. I live in the same area as NIH so it was not too inconvenient but very scary at first to think of being tested there. At that time I only had a choice of NIH, Mayo Clinic and a place in Quebec to do this then-rare pituitary surgery called a Transsphenoidal Resection.

My husband asked my endo if it were his wife, if he would recommend this surgery.  The endo responded that he was divorcing his wife – he didn’t care what happened to her.  Oh, my!

I chose NIH – closest and free. After I was interviewed by the doctors there, I got a letter that I had been accepted into the clinical trial.

The night before I was admitted, I signed my will.  I was sure I was going to die there.  If not during testing, as a result of surgery.

The first time I was there was for 6 weeks as an inpatient. More of the same tests.

There were about 12 of us there and it was nice not to be alone with this mystery disease. Many of these Cushies (mostly women) were getting bald, couldn’t walk, having strokes, had diabetes. One was blind, one had a heart attack while I was there. Several were from Greece.

My first roommate was a nurse.  She spent the entire first night screaming in pain.  I was very glad when they moved me to a new room!

Towards the end of my testing period, I was looking forward to the surgery just to get this whole mess over with – either a cure or dying. While I was at NIH, I was gaining about a pound a day!

During the time I was home the weekend  before surgery, a college classmate of mine (I didn’t know her) DID die at NIH of a Cushing’s-related problem. I’m so glad I didn’t find out until reading the alumnae magazine a couple months later!  She was the same class, same major, same home-town, same disease…

We have a Scottish doctor named James Lind to thank for the clinical trial.  He  conducted the first ever clinical trial in 1747 and developed the theory that citrus fruits cured scurvy.  Lind  compared the effects of various different acidic substances, ranging from vinegar to cider, on groups of afflicted sailors, and found that the group who were given oranges and lemons had largely recovered from scurvy after 6 days.

I’d like to think that I advanced the knowledge of Cushing’s at least a little bit by being a guinea  pig in 1987-1989.

From the NIH: http://endocrine.niddk.nih.gov/pubs/cushings/cushings.aspx

Hope through Research

Several components of the National Institutes of Health (NIH) conduct and support research on Cushing’s syndrome and other disorders of the endocrine system, including the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Child Health and Human Development (NICHD), the National Institute of Neurological Disorders and Stroke, the National Cancer Institute, and the National Center for Research Resources.

NIH-supported scientists are conducting intensive research into the normal and abnormal function of the major endocrine glands and the many hormones of the endocrine system. Researchers continue to study the effects of excess cortisol, including its effect on brain structure and function. To refine the diagnostic process, studies are under way to assess the accuracy of existing screening tests and the effectiveness of new imaging techniques to evaluate patients with ectopic ACTH syndrome. Researchers are also investigating jugular vein sampling as a less invasive alternative to petrosal sinus sampling. Research into treatment options includes study of a new drug to treat the symptoms of Cushing’s syndrome caused by ectopic ACTH secretion.

Studies are under way to understand the causes of benign endocrine tumor formation, such as those that cause most cases of Cushing’s syndrome. In a few pituitary adenomas, specific gene defects have been identified and may provide important clues to understanding tumor formation. Endocrine factors may also play a role. Increasing evidence suggests that tumor formation is a multistep process. Understanding the basis of Cushing’s syndrome will yield new approaches to therapy.

The NIH supports research related to Cushing’s syndrome at medical centers throughout the United States. Scientists are also treating patients with Cushing’s syndrome at the NIH Clinical Center in Bethesda, MD. Physicians who are interested in referring an adult patient may contact Lynnette Nieman, M.D., at NICHD, 10 Center Drive, Room 1-3140, Bethesda, MD 20892-1109, or by phone at 301-496-8935. Physicians interested in referring a child or adolescent may contact Constantine Stratakis, M.D., D.Sc., at NICHD, 10 Center Drive, Room 1-3330, Bethesda, MD 20892-1103, or by phone at 301-402-1998.

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