Ectopic Adrenocorticotropic Hormone-Secreting Pituitary Adenoma in the Clivus Region: A Case Report

Yan Zhang, Danrong Wu, Ruoqiu Wang, Min Luo, Dong Wang, Kaiyue Wang, Yi Ai, Li Zheng, Qiao Zhang, Lixin Shi

Department of Endocrinology and Metabolism, Guiqian International General Hospital, Guiyang, People’s Republic of China

Correspondence: Qiao Zhang; Lixin Shi, Department of Endocrinology and Metabolism, Guiqian International General Hospital, Guiyang, People’s Republic of China, Tel/Fax +86 851-86277666, Email endocrine_zq@126.com; slx1962@medmail.com.cn

Abstract: Ectopic pituitary adenoma (EPA) is a pituitary adenoma unrelated to the intrasellar component and is an extremely rare disease. EPA resembles typical pituitary adenomas in morphology, immunohistochemistry, and hormonal activity, and it may present with specific or non-specific endocrine manifestations. Here, we report a rare case of ectopic adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma in the clival region. Only three patients with ACTH-secreting pituitary adenomas occurring in the clivus have been previously reported, and the present case was diagnosed as a clivus-ectopic ACTH-secreting pituitary macroadenoma. Thus, in addition to the more common organs, such as the lung, thymus, and pancreas, in the diagnosis of ectopic ACTH syndrome, special attention should be paid to the extremely rare ectopic ACTH-secreting pituitary adenoma of the clivus region.

Keywords: ectopic pituitary adenoma, Cushing’s syndrome, clivus, adrenocorticotropic hormone, endocrine

Introduction

The diagnosis of Cushing’s syndrome (CS), particularly its localization diagnosis, has always been a challenge in clinical practice.1,2 Endogenous CS can be divided into adrenocorticotropic hormone (ACTH)-dependent and non-ACTH dependent with the former accounting for 70% of CS cases. Ectopic ACTH syndrome accounts for 5–10% of CS cases, and its lesions are mainly located in the lungs, thymus, pancreas, and the thyroid gland.3 Finding such lesions in non-pituitary intracranial regions is extremely rare, and ectopic ACTH in the clivus region is even rarer. To date, less than 60 cases of ectopic ACTH-secreting pituitary adenomas have been reported,4 and determining their localization is a formidable challenge in CS diagnosis. It is difficult to make an accurate and prompt diagnosis of ectopic ACTH-secreting pituitary adenoma caused by hypercortisolism based on its clinical manifestation, routine laboratory tests, and radiologic examinations.1,4 Ectopic pituitary adenomas (EPAs) are mainly concentrated in the sphenoid sinus, suprasellar region, and cavernous sinus, and rare regions include the clivus, ethmoid sinus, and nasal cavity.5 A literature review showed that only three cases of primary EPA in the clivus region have been reported worldwide.6–8 Recently, we diagnosed a patient with ectopic ACTH-secreting pituitary macroadenoma in the clivus region that was confirmed by surgery and immunohistochemistry.

Case Presentation

A 53-year-old female patient sought medical attention at our hospital for hypertension, headache, and dizziness with a blood pressure as high as 180/100 mmHg. Her medical history showed that she had developed similar symptoms 2 years ago. At that time, she had hypertension (180/100 mmHg), headache, and dizziness, and she was treated with amlodipine (5 mg per day), benazepril hydrochloride (10 mg per day), and metoprolol tartrate (50 mg per day). The patient was not hospitalized for treatment and did not undergo systemic examination. Three months before admission, the patient had a thoracic vertebrae fracture caused by moving heavy objects. One month before admission, she had a bilateral rib fracture due to falling on flat ground. Her physical examination results were as follows: blood pressure, 160/85 mmHg; height, 147 cm; weight, 55.2 kg; and body mass index (BMI), 25.54 kg/m2. In the physical examination, moon facies, buffalo hump, concentric obesity, facial plethora, and large patches of ecchymosis at the blood sampling site were observed. Purple striae were absent below the axilla, abdomen, and limbs. Her hematological examination results were as follows: cortisol (COR) rhythm with 33.52 µg/dL (reference range: 4.26–24.85) at 8:00 AM, 34.3 µg/dL at 4:00 PM, and 33.14 µg/dL at 12:00 AM; 1 mg dexamethasone overnight suppression test indicated 22.21 µg/dL COR at 8:00 AM; 24 h urine COR was 962.16 µg/24 h (reference range: 50–437 µg/24 h); 8:00 AM ACTH at two different times was 74 pg/mL and 90.8 pg/mL (reference range: <46); high-dose dexamethasone suppression test (HDDST) was 21.44 µg/dL COR (serum COR level was not suppressed by more than 50%); serum potassium was 3.38 mmol/L (reference range: 3.5–5.5); insulin-like growth factor-1 (IGF-1) was 106.6 ng/mL (reference range: 84–236); serum luteinizing hormone (LH) was <0.07 IU/L (reference range: 1.9–12.5); serum follicle stimulating hormone (FSH) was 0.37 IU/L (reference range: 2.5–10.2); prolactin (PRL), testosterone, progesterone, and estradiol test results were normal; FT4 was 8.25 pmol/L (reference range: 10.44–24.38); TSH was 1.116 mIU/L (reference range: 0.55–4.78); oral glucose tolerance test (OGTT) indicated that fasting blood glucose was 6.3 mmol/L and 2-h blood glucose was 18.72 mmol/L; and glycated hemoglobin (HbA1c) was 7.1%. A bone mineral density test suggested osteoporosis (dual energy X-rays: L1-L4 T values were −3.4).

Magnetic resonance (MR) scans were performed using a SIGNA Pioneer 3.0T (GE Healthcare, Waukesha, WI, USA), and computed tomography (CT) scans were performed using a 256 slice CT scanner (Revolution CT; GE Healthcare, Waukesha, WI, USA). The enhanced MR scan of the sellar lesion showed a soft tissue mass with abnormal signals in the occipital bone clivus. T1WI showed an isointense signal, and T2WI showed an isointense/slightly hyperintense signal in a large area of approximately 30 mm × 46 mm. The lesion extended anteriorly to completely fill the entire sphenoidal sinus, and it was in a close proximity to the right internal carotid arteries. Significant invasion, liquefaction, and necrosis were not observed in the bilateral cavernous sinuses. Pituitary gland morphology was normal with a superoinferior diameter of 3.14 mm, and the pituitary gland was located in the center. An occipital bone clival space-occupying lesion was considered with a tendency of low malignancy and a possibility of chordoma (Figure 1A–C). Non-enhanced high-resolution CT scans of the nasal sinuses showed osteolytic destruction, and a soft tissue mass was observed in the occipital bone clivus. The mass had a large area of 20 mm × 30 mm × 46 mm (Figure 1D). Enhanced CT of the adrenals showed bilateral adrenal gland hyperplasia.

Figure 1 (A) MR T1+T2 scan (transverse view). MR T1 scan (left) shows the soft tissue mass of the occipital clivus (white arrow), and MR T2 scan (right) shows that the right internal carotid artery, cavernous sinus, and tumor are within close proximity to each other (white arrow). (B) MR T1 enhanced scan (sagittal view) shows clear demarcation between normal pituitary gland and mass (white arrow). (C) MR T2 scan (sagittal view) shows that the pituitary fossa is normally present (white arrow). (D) CT (sagittal view) shows bony destruction of dorsum sellae, clivus, and sphenoid sinus by mass (white arrow).

Bilateral inferior petrosal sinus sampling (IPSS) combined with a desmopressin stimulation test had the following results: baseline ACTH at left inferior petrosal sinus/periphery (IPS/P), 5.4; post-stimulation IPS/P, 3.42; stimulation corrected (ACTHPRL) IPS/P, 2.8; right baseline IPS/P, 1.64; post-stimulation IPS/P, 9.34; and stimulation corrected IPS/P, 6.92. The left inferior petrosal sinus was the dominant side (Table 1).

Table 1 Bilateral Inferior Petrosal Sinus Sampling Combined with Desmopressin Stimulation Test

The patient underwent endoscopic transsphenoidal clival lesion resection surgery, and the postoperative pathology test results showed EPA (Figure 2). The immunohistochemistry staining results were as follows: CK (+), SYN (+), CgA (+), ACTH (+), growth hormone (GH) (−), LH (−), TSH (−), PRL (−), FSH (−), and Ki-67 (<1% +). The COR level at 10 days after surgery was 15.87 µg/dL, and the ACTH level was 31.37 pg/mL (Table 2).

Table 2 Changes in COR and ACTH Levels During Course of Treatment
Figure 2 Pathological diagnosis of (clivus) ectopic pituitary adenoma. (A) Pituitary adenoma revealing a trabecular and nested structure revealing vascular invasion (hematoxylin and eosin (HE) stain, 200x) composed of two distinct types of cells. (B) ACTH expression in the EPA (200x, ACTH-antibody, Dako).

After admission, her blood and urine COR levels were significantly elevated, and a qualitative diagnosis of CS was obtained. Etiological examination found that ACTH was also significantly elevated, suggesting that the CS was ACTH dependent. The HDDST results showed that the serum COR level was not suppressed by more than 50% and was accompanied by hypokalemia, suggesting that the ACTH-dependent CS may be ectopic ACTH syndrome. Ectopic ACTH syndrome is relatively rare, and the lesions are caused by non-pituitary tumors. No lesions were identified in the lung, thymus, pancreas, and thyroid of our patient. Regarding the IPSS examination, the IPS/P ratio was greater than 2, which suggested that the ectopic ACTH was located intracranially and not at the periphery. Radiologic testing suggested that the pituitary structure was normal and that a space-occupying lesion in the clivus region was present. Therefore, ectopic ACTH-secreting adenoma in the clivus region was considered, and postoperative pathological biopsy was used to confirm the diagnosis.

Discussion

EPA is an extremely rare disease that occurs outside of the sella turcica, and it is not linked to the intrasellar pituitary. The morphology, immunohistochemistry, and hormone activity of EPAs are similar to typical pituitary adenomas. EPAs can manifest as specific or non-specific endocrine disorders, and they account for 0.48% of all pituitary adenomas.9 The pathogenesis of EPA is still currently unknown. It is generally considered that during the development of the anterior pituitary lobe, the incompletely degraded Rathke cleft cyst remnants of the Rathke pouch lead to the formation of EPAs in the nasopharynx, sphenoid, and clivus.10,11 EPA is rare in China. Zhu et al5 recorded 14,357 pituitary gland patients in the last 20 years; of these patients, only 14 were diagnosed with EPA (0.098% of all cases), but none of the lesions originated from the clivus region. Previous literature reviews4,5 revealed that non-functioning EPAs in the clivus region are the most common (50%); the most common hormone-secreting functional adenomas are PRL adenomas and GH adenomas, which account for 25.0% and 21.4% of EPAs, respectively, whereas ACTH-secreting EPAs are extremely rare and only account for 3.6% of cases.

The postoperative pathological and immunohistochemical results of the tumor tissue in the patient demonstrated that it was an ectopic ACTH-secreting pituitary macroadenoma in the clivus region. Most EPAs are microadenomas (diameter <1 cm), except those in the clivus region, which are macroadenomas.5 Adenoma size generally does not affect the patient’s clinical and biochemical characteristics, and it may be related to tumor location or extension.12 Encasement of the internal carotid artery is a characteristic feature of EPA invasion into surrounding tissues.5 Encasement of the right internal carotid artery by the tumor was also observed in our patient. Therefore, surgery cannot completely remove the tumor and may ultimately affect surgical outcomes, and radiotherapy may even be required in the future. The serum COR and ACTH levels of our patient were evaluated 10 days after surgery. Although the levels were significantly lower than those before the surgery, the COR level was still significantly higher than the cutoff value of 1 µg/dL,13,14 suggesting that the patient may not have complete remission due to the incomplete tumor resection in the area adjacent to the carotid artery during surgery. Another feature that was observed in our patient was bone invasion. Because the clivus is composed of abundant cancellous bone that is connected to surrounding bone structures, EPAs or other tumors may cause bone destruction and affect the sphenoidal sinus and cavernous sinus, which is also consistent with literature reports.15,16

Due to the low incidence of EPAs, most EPA cases are reported as case reports in the literature. We performed an English literature search using the PubMed and Web of Science Core Collection databases with the following predetermined terms: “Cushing’s syndrome”, “pituitary adenomas”, “clivus”, “ectopic pituitary adenoma”, and “adrenocorticotropic”. The literature was included if it met the following criteria: (i) the confirmed diagnosis of CS or ectopic ACTH syndrome was described in the literature; (ii) the diagnosis of EPA was confirmed by postoperative inspection; and (iii) EPA occurred in the clivus. After excluding cases of clival invasion from other sites, we found only three reports of ectopic ACTH-secreting adenoma in the clivus region,6–8 and they were all female patients. Ortiz-Suarez and Erickson6 employed transfrontal craniotomy to demonstrate that the ectopic ACTH-secreting adenoma was an extension of extrasellar lesion to the clivus. In a case report by Pluta et al,7 the patient was found to have cavernous sinus and clival ACTH-positive tumors through transphenoidal surgery. In a case report by Aftab et al,8 the patient only presented a space-occupying lesion with unilateral vision loss; the patient was initially diagnosed with clival chordoma, but the postoperative results supported the diagnosis of EPA. Based on preoperative imaging, the possibility of chordoma was also considered to be high in our patient. We combined the clinical manifestation and laboratory test results of the patient and considered the etiology of CS to conclude that the patient had clival ectopic ACTH-secreting adenoma instead of chordoma.

Hormone tests in our patient suggested secondary pituitary-gonadal axis and decreased pituitary-thyroid axis function. These changes in endocrine function may be due to pituitary suppression by hypercortisolism. After surgery, the corresponding markers recovered, indicating that the suppression was transient. The patient has a history of fracture and a bone mineral density suggestive of osteoporosis, which may also be associated with CS hypercortisolemia.

Treatment modalities for EPA include adenoma resection surgery, radiotherapy, and drugs. The first-line recommended treatment is surgical resection. Craniotomy is considered the surgical procedure of choice for EPA, and endoscopic transsphenoidal surgery (TSS) is considered a feasible method for preserving pituitary function while simultaneously treating EPA. However, due to limitations with the surgical operation space, there are still concerns whether sufficient exploration and effective tumor resection can be achieved.17 Because there are few case reports of such patients, the long-term outcomes of these two surgical procedures require further validation. Due to differences in EPA sites and functions, the efficacy of surgery also differs. Zhu et al5 reported that compared to the radical resection rate of sphenoidal sinus and cavernous sinus EPA (72.3% and 73.3%, respectively), the radical resection rate of clival EPA is only 45.0%, and this difference is statistically significant.

The three clival EPA patients described in the three relevant publications6–8 all showed significant improvements in postoperative signs, symptoms, and hormone levels after complete surgical removal of the lesions or combined with radiation therapy. In our patient, however, radical resection of the tumor could not be achieved due to the close proximity of the tumor mass to the right internal carotid artery, and surgery could not be used to achieve complete remission, which is similar to the case reported by Zhu et al.5 For such patients, radiotherapy can be considered as a second-line treatment for EPA. To control hormone levels, drugs and bilateral adrenalectomy are also treatment options.5,18,19

Conclusion

EPA is a rare disease, and clival EPA is even rarer. From the entire diagnosis and treatment course, this unique and rare EPA case was preliminarily diagnosed through a comprehensive hormone panel and IPSS, and it was confirmed by pathology and immunohistochemistry after surgery. In the diagnosis of ectopic ACTH syndrome, attention should also be paid to extremely rare pituitary ectopic sites, such as the sphenoid sinuses, parasellar region, and the clivus, in addition to common sites, such as the lungs, thymus, pancreas, and thyroid.

Data Sharing Statement

The raw data supporting the conclusions of this article will be made available by the authors without undue reservation.

Informed Consent Statement

Prior written permission was obtained from the patient for treatment as well as for the preparation of this manuscript and for publication. Our institution approved the publication of the case details.

Acknowledgments

We would like to thank the patient and her family.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

There is no funding to report.

Disclosure

The authors report no conflicts of interest in this work.

References

1. Senanayake R, Gillett D, MacFarlane J, et al. New types of localization methods for adrenocorticotropic hormone-dependent Cushing’s syndrome. Best Pract Res Clin Endocrinol Metab. 2021;35:101513. doi:10.1016/j.beem.2021.101513

2. Young J, Haissaguerre M, Viera-Pinto O, et al. Management of Endocrine Disease: cushing’s syndrome due to ectopic ACTH secretion: an expert operational opinion. Eur J Endocrinol. 2020;182:R29–r58. doi:10.1530/EJE-19-0877

3. Hayes AR, Grossman AB. The ectopic adrenocorticotropic hormone syndrome: rarely easy, always challenging. Endocrinol Metab Clin North Am. 2018;47:409–425. doi:10.1016/j.ecl.2018.01.005

4. Zhu J, Lu L, Yao Y, et al. Long-term follow-up for ectopic ACTH-secreting pituitary adenoma in a single tertiary medical center and a literature review. Pituitary. 2020;23:149–159. doi:10.1007/s11102-019-01017-y

5. Zhu J, Wang Z, Zhang Y, et al. Ectopic pituitary adenomas: clinical features, diagnostic challenges and management. Pituitary. 2020;23:648–664. doi:10.1007/s11102-020-01071-x

6. Ortiz-Suarez H, Erickson DL. Pituitary adenomas of adolescents. J Neurosurg. 1975;43:437–439. doi:10.3171/jns.1975.43.4.0437

7. Pluta RM, Nieman L, Doppman JL, et al. Extrapituitary parasellar microadenoma in Cushing’s disease. J Clin Endocrinol Metab. 1999;84:2912–2923. doi:10.1210/jcem.84.8.5890

8. Aftab HB, Gunay C, Dermesropian R, et al. “An Unexpected Pit” – ectopic pituitary adenoma. J Endocr Soc. 2021;5:A557–A558. doi:10.1210/jendso/bvab048.1137

9. Li X, Zhao B, Hou B, et al. Case report and literature review: ectopic thyrotropin-secreting pituitary adenoma in the suprasellar region. Front Endocrinol. 2021;12:619161. doi:10.3389/fendo.2021.619161

10. Agely A, Okromelidze L, Vilanilam GK, et al. Ectopic pituitary adenomas: common presentations of a rare entity. Pituitary. 2019;22:339–343. doi:10.1007/s11102-019-00954-y

11. Tajudeen BA, Kuan EC, Adappa ND, et al. Ectopic pituitary adenomas presenting as sphenoid or clival lesions: case series and management recommendations. J Neurol Surg B Skull Base. 2017;78:120–124. doi:10.1055/s-0036-1592081

12. Akirov A, Shimon I, Fleseriu M, et al. Clinical study and systematic review of pituitary microadenomas vs. macroadenomas in cushing’s disease: does size matter? J Clin Med. 2022;11:1558. doi:10.3390/jcm11061558

13. Badiu C. Williams textbook of endocrinology. Acta Endocrinologica. 2019;15:416. doi:10.4183/aeb.2019.416

14. Rollin GA, Ferreira NP, Junges M, et al. Dynamics of serum cortisol levels after transsphenoidal surgery in a cohort of patients with Cushing’s disease. J Clin Endocrinol Metab. 2004;89:1131–1139. doi:10.1210/jc.2003-031170

15. Hu S, Cheng S, Wu Y, et al. A large cavernous sinus giant cell tumor invading clivus and sphenoid sinus masquerading as meningioma: a case report and literature review. Front Surg. 2022;9:861739. doi:10.3389/fsurg.2022.861739

16. Wu X, Ding H, Yang L, et al. Invasive corridor of clivus extension in pituitary adenoma: bony anatomic consideration, surgical outcome and technical nuances. Front Oncol. 2021;11:689943. doi:10.3389/fonc.2021.689943

17. Sun X, Lu L, Feng M, et al. Cushing syndrome caused by ectopic adrenocorticotropic hormone-secreting pituitary adenomas: case report and literature review. World Neurosurg. 2020;142:75–86. doi:10.1016/j.wneu.2020.06.138

18. Szabo Yamashita T, Sada A, Bancos I, et al. Differences in outcomes of bilateral adrenalectomy in patients with ectopic ACTH producing tumor of known and unknown origin. Am J Surg. 2021;221:460–464. doi:10.1016/j.amjsurg.2020.08.047

19. Szabo Yamashita T, Sada A, Bancos I, et al. Bilateral adrenalectomy: differences between cushing disease and Ectopic ACTH-producing tumors. Ann Surg Oncol. 2020;27:3851–3857. doi:10.1245/s10434-020-08451-4

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Psoriatic arthritis patients face more endocrine comorbidities


AT 2016 GRAPPA ANNUAL MEETING


VITALS

Key clinical point:Patients with psoriatic disease had a significantly higher prevalence of diabetes mellitus and some other endocrine comorbidities.

Major finding: In a univariate analysis, the risk for Cushing’s disease was notably higher among psoriatic arthritis patients, compared with controls (odds ratio, 5.31).

Data source: Retrospective, cross-sectional comparison of 3,161 patients with psoriatic arthritis and 31,610 matched controls.

Disclosures: Dr. Haddad, Dr. Coates, and Dr. Kavanaugh reported having no relevant financial disclosures.

The large, population-based cohort is a strength of the study. “We are now going back to see how many of these patients were seen by rheumatologists,” Dr. Haddad said. A lack of association with disease burden is a potential limitation, he added.

Thirty percent of patients were treated with biologics and about 67% with steroids. “That number treated with steroids seems high,” a meeting attendee commented. Dr. Haddad explained that it is the percentage ever treated with steroids, not necessarily currently on steroids.

In a separate session at the GRAPPA meeting addressing psoriatic disease treatment recommendations, an attendee asked about specific recommendations for comorbidities. For now, GRAPPA plans to include comorbidities within its overall recommendations, as it did in its most recent update, released in January 2016. A limited amount of data is a primary reason.

“As the evidence on comorbidities gets better, we may someday have separate recommendations for comorbidities,” said Laura Coates, MD, a clinical lecturer in rheumatology at the University of Leeds (England).

“The comorbidities are very important,” said Arthur F. Kavanaugh, MD, professor of medicine at the University of California, San Diego. “That’s trickier and deals with the international nature of GRAPPA. It’s hard to say, ‘Go see this specialist,’ because that might not be standard of care in that country.”

Dr. Haddad, Dr. Coates, and Dr. Kavanaugh reported having no relevant financial disclosures.

 From http://www.clinicalendocrinologynews.com/specialty-focus/diabetes/single-article-page/psoriatic-arthritis-patients-face-more-endocrine-comorbidities/f8700c8ffde9fc2534295458feb8eba3.html?utm_source=News_CEN_eNL_072616&utm_medium=email&utm_content=Psoriatic+arthritis+patients+face+more+endocrine+comorbidities

Pituitary Gland: Normal Function and Assessment

Abstract

This computer-based, interactive module introduces preclinical medical students to normal pituitary function and outlines its assessment. Solid understanding of these topics is requisite to learning clinical disorders of the pituitary.

Existing resources largely target learners at earlier or later stages of training; thus, we created this resource to address needs of medical students during a first- or second-year endocrine course. A module format was selected to promote interactive, independent learning.

Two cohorts of medical students completed the 40-minute module: 172 second-year students who had completed a year of basic sciences in the traditional curriculum and 180 foundation-phase students in a three-semester combined basic and clinical sciences curriculum (due to a change in the medical school curriculum at our institution). In both instances, the module was completed before start of clinical pituitary content. A static set of PowerPoint slides accompanied the module to facilitate note taking.

Test Your Knowledge slides were inserted to ensure grasp of key terms/concepts before moving to subsequent slides. A short question-and-answer session was held following module completion to clarify points of confusion. Students rated effectiveness of the module as 4.6 out of 5, commenting on its clarity, organization, high-yield nature, and utility in preparing for clinical material.

Faculty noted greater understanding of foundational pituitary principles and more engaging discussions. The percentage of pituitary-related questions answered correctly on the midterm exam increased.

Finally, success of the pituitary module prompted development of adrenal, thyroid, and parathyroid modules that now comprise the Endocrine Organs Introduction Series in our curriculum.

Citation

Kirk D, Smith KW. Pituitary gland: normal function and assessment. MedEdPORTAL Publications. 2016;12:10430. http://dx.doi.org/10.15766/mep_2374-8265.10430

Educational Objectives

After completing this module, the learner will be able to:

  1. Describe the normal function and regulation of the pituitary gland, including names and actions of the anterior and posterior pituitary hormones.
  2. Understand the basic approach to laboratory assessment of the pituitary.
  3. Differentiate between anterior and posterior pituitary origin, function, and regulation.
  4. List the hormones produced by the pituitary gland.
  5. Discuss for each pituitary hormone: hypothalamic stimulating/inhibiting factors and their clinical uses, basic physiologic function, and regulation (feedback loop).
  6. Describe factors that affect growth hormone levels.
  7. Understand the tests for growth hormone excess and deficiency.
  8. Define a primary versus secondary endocrine disorder.

Keywords

  • Endocrine, Endocrinology, Pituitary, Module, Preclinical Medical Education

More information at https://www.mededportal.org/publication/10430

Cushing’s Tips

Things I’ve learned and wanted to share

By LindaP, with a little help from other Cushing’s Message Board members. This is a continuing list, if you want to share.

I have learned so much on this Cushing’s journey, much of it from all of you and this site. I wanted to share those learnings, in the event that it helps anyone else.

Obviously – my own opinions here!

My best wishes to everyone on their Cushing’s journey.

Linda

**********************************************

1. Trust your instincts.

2. Trust your instincts some more.

3. Do your research – read everything you can, talk to people, use this website and the message boards. Slog through research papers. Not all of it will make sense, but it is amazing how much you can learn, and how much it will help you on your diagnostic journey.

4. Not everyone will have every one of the “typically described” symptoms of the hump, moon face, straie, and central obesity. Some people get them all, some people get some, and others don’t develop these signs.

5. While substantial weight gain is very common with Cushings, there are some people who have only mild or moderate weight gain. What seems to be the common thread, however, is the inability to lose it in spite of diet and exercise.

6. You don’t need to test positive on every single test, or test positive on every type of test, to have Cushings. There is substantial variation in how we present with the disease, and in which tests will identify the excess cortisol in our bodies. Do not let a single negative result on any one test, or negative results on a particular type of test, prevent you from aggressively pursuing a Cushings diagnosis if there is strong suspicion. For example, it is possible for an individual to have proven Cushings without ever having a positive on a ufc or dex suppression test.

7. Do not waste time, energy and financial resources on unhelpful doctors.

8. Whenever possible, get to a true Cushings expert as soon as the disease is suspected.

9. When seeing a new endocrinologist, don’t be afraid to ask:

a. What is your opinion on cyclic or intermittent Cushings?b. When and how might you diagnose a mild or early case of Cushings? Do you recommend treatment in those cases?

c. Do you believe it is possible for someone to have Cushings without all or some of the commonly associated stigmata (straie, hump, moon face, substantial weight gain)?

d. What is your diagnostic criteria for Cushings?

i. Lab tests

ii. Physical symptoms

iii. Imaging

e. How many patients have you diagnosed with Cushings?

f. What surgeon(s) do you recommend and work with for your patients with tumors that are causing Cushings?

g. If Cushings is suspected, how can we work together to maximize testing to give us answers as quickly as possible? How can I most easily get my test results from your office?

10. Make sure your doctor is willing to support the amount of testing that may be necessary to allow you to begin to distinguish between high and low periods. Make sure your doctor is also willing to support multiple types of tests to appropriately rule in/out Cushings.

11. Create a binder and get copies of every single test. (Make additional copies of test results so that you have extra available to perhaps send in advance to a new doctor, or to be able to readily provide a copy during your appointment as necessary). Get copies of clinic notes as well. Organize them into the binder. My binder has the following tabs:

a. Spreadsheet that summarizes most relevant test resultsb. Current medical history/summary of symptoms

c. Imaging reports

d. Cortisol test results (serum, salivary, ufcS)

e. Other lab results (including EKGs and other relevant tests)

f. Eyes (visual field tests, letter from eye doctor, etc)

g. Clinic Notes

12. Research tests. It is not uncommon for a test to be ordered or interpreted incorrectly.

13. MRIs are only tools. They can be interpreted differently by different people and they may not accurately identify the extent or location of a tumor.

14. Create a spreadsheet, or use a journal, to track symptoms daily. Log test results so that you can begin to see patterns. Symptoms may be as subtle as canker sores, or cracked lips or skin, a single pimple, or may be more obvious such as severe swings in mood and energy levels, insomnia, bad acne, etc. Write it all down and track it.

15. Test whenever you feel different.

16. Symptoms of a high for you may or may not match what is typically described for a high. You may experience a high differently. For example, achiness is frequently described as a low symptom, but it may occur during a high in your case. Tracking symptoms and correlating test results help to identify patterns of a high.

17. Start testing your own blood sugar to identify any possible blood sugar problems and to look for possible correlation between episodes of high blood sugar and high cortisol levels. This won’t apply to everyone, and may not be useful in your case, but it was very helpful to me. A very good Walgreen’s brand glucometer is only $20.

18. Get a blood pressure cuff and start checking your own bp at home. Look for patterns there as well.

19. Summarize test results for your doctor (PCP, endocrinologist, or even surgeon). Create a simple table that shows your relevant test results over time.

20. Collect photos that illustrate how your physical appearance has changed.

21. When researching surgeons, learn as much as you can about the different techniques and approaches. Some may seem similar, but there are differences that are important to understand.

22. When interviewing surgeons, the following questions may be helpful (mostly pituitary focused):

a. How will you approach the tumor?

b. What instruments are used? Endoscope? Microscope? Both?

c. What incisions are made?

d. Do you need to clear any kind of path within the nasal or sinus area for your instruments? How will you do that?

e. What stitches will I have?

f. Do you use a “fat plug”?

g. Do you use a lumbar drain?

h. Will there be any nasal packing?

i. How will my head be immobilized during surgery? (Is a “halo” used?)

j. Do you use Doppler to localize the carotid arteries? (not necessary in fully endoscopic procedure as I understand it)

k. Describe your approach to locating any tumor seen on the MRI, and what you will do to find any other tumors that may be in, on, or around the gland.

l. Under what circumstances might you find it necessary to remove either part of the pituitary gland, or all of it?

m. How many of these procedures have you done?

n. How long have you been performing this particular procedure?

o. What are some typical complications that occur with this procedure? How do you manage those complications?

p. Based on my MRI, is there anything in particular that might suggest greater risk of diabetes insipidous or other long term complications with this surgery?

q. Tell me what to expect in terms of post-operative pain and how it will be managed.

r. Is an ICU stay typically necessary?

s. How long can I expect to stay in the hospital?

t. Do you give steroids intra-operatively?

u. When do you test post-op cortisol levels? What is the cortisol replacement therapy protocol? If my endocrinologist is out of state, who will be monitoring that part of my testing and prescribing cortisol replacement as necessary?

v. When can I travel to return home?

w. What restrictions will I have once discharged? (Lifting, noseblowing, how I sleep, driving, exercise, etc)

x. How do I contact you if I should have any problems or concerns once discharged?

y. How will you communicate with my endocrinologist regarding the results of my surgery?

z. What is your protocol for following up with patients post-operatively?

aa. What is your rate of post-operative sinus infection?

bb. What is your rate of post-operative diabetes insipidous, both temporary and long-term?

23. These questions for your endocrinologist may be helpful once surgery is planned:

a. How will you determine my post-op cortisol replacement needs?

b. At what point will you recommend that I begin tapering my dose? What are your guidelines for each step in the weaning process?

c. Based on my case and your experience with other Cushings patients, what might I experience during the recovery period? How long before I feel “better”? What restrictions will I have?

d. When and how will you determine if other pituitary functions should be tested post-op? How will you test other pituitary functions post-op?

e. Do you provide a prescription for emergency injectable hydrocortisone?

f. Do you provide written instructions I may carry for Emergency Room staff in the event that I have an adrenal crisis?

g. How long should I expect to be off work?

h. How will you follow up with me post-op?

i. What is the best way to reach you if I have any questions or concerns after surgery?

24. Participate on the Cushings Boards to support yourself and others through the Cushings diagnosis and treatment journey. (You’ll also make some new friends.)

NIH Cushing’s Clinical Trials

Rank Status Study
1 Recruiting Safety and Efficacy of LCI699 in Cushing’s Disease Patients

Condition: Cushing Disease
Intervention: Drug: LCI699
2 Recruiting Preoperative Bexarotene Treatment for Cushing’s Disease

Condition: Cushing’s Disease
Intervention: Drug: Bexarotene
3 Recruiting Rosiglitazone in Treating Patients With Newly Diagnosed ACTH-Secreting Pituitary Tumor (Cushing Disease)

Condition: Brain and Central Nervous System Tumors
Interventions: Drug: rosiglitazone maleate;   Other: laboratory biomarker analysis
4 Unknown  Study of Depression, Peptides, and Steroids in Cushing’s Syndrome

Condition: Cushing’s Syndrome
Intervention:
5 Recruiting Examination of Brain Serotonin Receptors in Patients With Mood Disorders

Conditions: Mood Disorder;   Bipolar Disorder;   Depression
Intervention:
6 Recruiting An Investigation of Pituitary Tumors and Related Hypothalmic Disorders

Conditions: Abnormalities;   Craniopharyngioma;   Cushing’s Syndrome;   Endocrine Disease;   Pituitary Neoplasm
Intervention:
7 Recruiting Prospective, Open-Label, Multicenter, International Study of Mifepristone for Symptomatic Treatment of Cushing’s Syndrome Caused by Ectopic Adrenal Corticotrophin Hormone (ACTH) Secretion

Condition: Cushing’s Syndrome
Intervention: Drug: Mifepristone
8 Recruiting Anesthesia Management of Retroperitoneal Adrenalectomies

Condition: Adrenal Tumors
Intervention:
9 Recruiting Defining the Genetic Basis for the Development of Primary Pigmented Nodular Adrenocortical Disease (PPNAD) and the Carney Complex

Conditions: Cushing’s Syndrome;   Hereditary Neoplastic Syndrome;   Lentigo;   Neoplasm;   Testicular Neoplasm
Intervention:
10 Recruiting New Imaging Techniques in the Evaluation of Patients With Ectopic Cushing Syndrome

Condition: Cushing Syndrome
Intervention:
11 Recruiting Adolescence, Puberty, and Emotion Regulation

Conditions: Mood Disorder;   Neurobehavioral Manifestation;   Healthy
Intervention:
12 Recruiting Insulin Sensitivity and Substrate Metabolism in Patients With Cushing’s Syndrome

Conditions: Cushing’s Syndrome;   Insulin Resistance
Intervention: Procedure: Surgery
13 Recruiting Study of Adrenal Gland Tumors

Condition: Adrenal Gland Neoplasm
Intervention:
14 Not yet recruiting Adrenalectomy Versus Follow-up in Patients With Subclinical Cushings Syndrome

Condition: Adrenal Tumour With Mild Hypercortisolism
Intervention: Procedure: Adrenalectomy
15 Recruiting Assessing Fertility Potential in Female Cancer Survivors

Condition: History of Cancer
Intervention:
16 Recruiting Study of Pasireotide in Patients With Rare Tumors of Neuroendocrine Origin

Conditions: Pancreatic Neoplasm;   Pituitary Neoplasm;   Nelson Syndrome;   Ectopic ACTH Syndrome
Intervention: Drug: Pasireotide LAR
17 Recruiting Adrenal Tumors – Pathogenesis and Therapy

Conditions: Adrenal Tumors;   Adrenocortical Carcinoma;   Cushing Syndrome;   Conn Syndrome;   Pheochromocytoma
Intervention:
18 Recruiting Prevalence of Pituitary Incidentaloma in Relatives of Patients With Pituitary Adenoma

Condition: Pituitary Tumor
Intervention:
19 Recruiting Safety and Effectiveness of Granulocyte Transfusions in Resolving Infection in People With Neutropenia (The RING Study)

Conditions: Neutropenia;   Infection
Interventions: Drug: Standard antimicrobial therapy;   Biological: Granulocyte transfusions;   Drug: G-CFS/dexamethasone;   Device: Apheresis machine
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