8 medical conditions that could cause sudden weight gain

Weight gain can be associated with hormonal conditions, mood disorders, or other physiological factors. A sudden and unexplained weight gain could be your body’s way of signalling an underlying medical issue that needs to be addressed. For the sake of health and long-term well-being, it is important to differentiate between a few harmless extra kilos and a fluctuation that could be hiding a bigger problem. You can only be certain after consulting a healthcare practitioner.

If the weighing scale says your numbers are up but you haven’t changed your eating and exercise habits, you might consider any of the 8 medical conditions:

1.     Hypothyroidism The American Thyroid Association reveals that one in eight women will develop a thyroid disorder during her lifetime. Hypothyroidism refers to an underactive thyroid. The thyroid controls several body functions and your metabolism is one of them. If you’re not producing enough thyroid hormone your body can’t burn as much energy. Symptoms appear throughout your system. They include: weight gain, exhaustion, drier skin, thinner hair, bloating, muscle weakness, constantly feeling cold, and constipation. Once diagnosis is confirmed a doctor can prescribe an oral replacement for thyroid hormone that can relieve symptoms within weeks.

2.     Polycystic ovary syndrome (PCOS) One in 10 women of childbearing age undergoes PCOS. It is an endocrine disorder characterised by an imbalance in the sex hormones oestrogen and testosterone.  This results in irregular periods, acne and even facial hair growth. The disorder also disrupts the way the body uses insulin — which is the hormone responsible for converting carbohydrates into energy. As a result the sugars and starches you consume are stored as fat instead of energy, thus, weight gain. PCOS has no cure but women who have it can manage their symptoms with lifestyle changes and medication. A doctor’s consultation will help you find an appropriate method.

3. Insomnia Avoid fake news! Subscribe to the Standard SMS service and receive factual, verified breaking news as it happens. Text the word ‘NEWS’ to 22840 Sleep deprivation can negatively impact both your metabolism and your hunger hormones. Sleeping too little increases ghrelin, the hormone that signals the body that it’s time to eat, while lowering leptin, the hormone that says you are full. The result: increased cravings and snacking to get more energy through the day. Insomnia increases impulsive eating. A 2018 study published in the American Journal of Clinical Nutrition found that the right amount of sleep could mean consuming up to 10 fewer grams of sugar throughout the day.

4.     Tumours Weight gain around your belly as opposed to your lower body or other areas can be more dangerous to your health. Large pelvic area tumours like uterine or ovarian tumours can inflate the abdomen the way excess fat does. In some cases they can also be cancerous. In addition to weight gain, symptoms of ovarian or uterine tumours include vaginal bleeding, lower back pain, constipation and painful intercourse. But these signs are common for other conditions as well so it‘s worth confirming with a doctor to rule out any possible complications.

5. Peri menopause and menopause Perimenopause -the transition period to menopause can start as early as a woman’s mid-thirties, but usually starts in their forties. This period triggers hormones like oestrogen to rise and fall unevenly, which can cue weight gain in some women. Genetics are a good starting point on how your body experiences these changes, so it would be helpful to look into how it affected your mother and other older women in your family. Other signs of perimenopause are mood swings, irregular periods, hot flashes, and changes in libido. Age also contributes to loss of muscle mass and increase in body fat. An Ob-Gyn should be able to talk you through these changes and recommend management options.

6.     Mood disorders Depression and anxiety can result in fatigue, lack of focus and irritability. Some people cope with anxious or sad feelings by mindlessly munching on food they don’t really need. Additionally chronic stress throws your body into fight-or-flight mode, leading to a surge of adrenaline, as well as a heavy dose of the hormone cortisol –responsible for restoring energy reserves and storing fat.

7. Cushing syndrome Sometimes tumours on the pituitary or adrenal glands can contribute to a condition known as Cushing’s disease which is characterised by high levels of cortisol in the blood. Taking long term steroids could also result in this disease. Patients with Cushing syndrome will experience rapid weight gain in the face, abdomen and chest. They also display slender arms and legs compared to the heavy weight in the core of the body. Other symptoms include: high blood pressure, mood swings, osteoporosis, discoloured stretch marks, acne, and fragile skin. Depending on the cause, Cushing‘s disease can be treated in a different ways.

8. New medication Before starting on any new prescription medication, ask your doctor if weight gain is a possible side effect. Birth control pills may lead to weight gain depending on the brand, dosage, and the person’s hormonal levels. Psychiatric medications, especially for depression and bipolar disorder, have been known to cause weight gain, as they target the brain. Similarly, taking insulin to manage diabetes or medications that treat high blood pressure can also lead to extra kilos, so staying active and sticking to a strict meal plan can help you take insulin without unnecessarily weight gain.

Adapted from https://www.standardmedia.co.ke/lifestyle/article/2001297348/8-medical-conditions-that-could-cause-sudden-weight-gain

Cushing Syndrome Results in Poor Quality of Life Even After Remission

Functional remission did not occur in most patients with Cushing syndrome who were considered to be in biochemical and clinical remission, according to a study published in Endocrine. This was evidenced by their quality of life, which remained impaired in all domains.

The term “functional remission” is a psychiatric concept that is defined as an “association of clinical remission and a recovery of social, professional, and personal levels of functioning.” In this observational study, investigators sought to determine the specific weight of psychological (anxiety and mood, coping, self-esteem) determinants of quality of life in patients with Cushing syndrome who were considered to be in clinical remission.

The cohort included 63 patients with hypercortisolism currently in remission who completed self-administered questionnaires that included quality of life (WHOQoL-BREF and Cushing QoL), depression, anxiety, self-esteem, body image, and coping scales. At a median of 3 years since remission, participants had a significantly lower quality of life and body satisfaction score compared with the general population and patients with chronic diseases. Of the cohort, 39 patients (61.9%) reported having low or very low self-esteem, while 16 (25.4%) had high or very high self-esteem. Depression and anxiety were seen in nearly half of the patients and they were more depressed than the general population. In addition, 42.9% of patients still needed working arrangements, while 19% had a disability or cessation of work.

Investigators wrote, “This impaired quality of life is strongly correlated to neurocognitive damage, and especially depression, a condition that is frequently confounded with the poor general condition owing to the decreased levels of cortisol. A psychiatric consultation should thus be systematically advised, and [selective serotonin reuptake inhibitor] therapy should be discussed.”

Reference

Vermalle M, Alessandrini M, Graillon T, et al.  Lack of functional remission in Cushing’s Syndrome [published online July 17, 2018]. Endocrine. doi:10.1007/s12020-018-1664-7

From https://www.endocrinologyadvisor.com/general-endocrinology/functional-remission-quality-of-life-cushings-syndrome/article/788501/

Cushing’s Syndrome Eludes Treatment Paradigm or Standard Approach to Care

Results of two systematic reviews indicate that while surgery is the preferred treatment, many patients present with contraindications without an accepted management paradigm leaving clinicians to follow a patient-centric approach to care.

With commentary by Eliza B. Geer, MD

Cushing’s syndrome may arise from an endogenous glucocorticoid excess is either adrenocorticotropic hormone (ACTH)-dependent or ACTH-independent; each variation has numerous underlying causes, including pituitary tumor, adrenal tumor, or other unknown causes.

Although rare, ectopic Cushing’s syndrome results from a non-pituitary ACTH-producing source. Cushing’s disease, a type of Cushing’s syndrome, affects an estimated 1.2 to 2.4 million people each year, and is caused by an ACTH-secreting pituitary adenoma.1

While surgery is preferred for treatment of Cushing's syndrome many patients need a medical approach instead.

Gaining insights into treatment preferences and efficacy for Cushing’s syndrome were the focus of two separate systematic reviews and meta-analyses, both published in the journal, Pituitary: one regarding medical treatments for Cushing’s syndrome,2 and the other comparing endoscopic versus microscopic transsphenoidal surgery for Cushing’s disease.3

Assessing Medical Management of Cushing’s Syndrome

The meta-analysis examining medical care of individuals with Cushing’s syndrome encompassed 1520 total patients across 35 studies, most of whom had Cushing’s disease.2 However, only 2 of the 35 studies were randomized trials, highlighting the lack of and clear need for controlled clinical trials on medical therapies for Cushing’s syndrome.

Surgery is typically first-line treatment—whether transsphenoidal pituitary adenomectomy for Cushing’s disease,4 removal of the ACTH-producing tumor in ectopic Cushing’s syndrome or adrenalectomy in ACTH-independent Cushing’s syndrome.5

However, many patients require medical therapy owing to contraindications for surgery, for recurrent disease, or to control cortisol secretion prior to surgery or radiotherapy. Results of the meta-analysis reflected wide-ranging normalization of cortisol levels depending upon the agent used– from 35.7% for cabergoline to nearly 82% for mitotane in Cushing’s disease.2 Combination therapy (medications used either together or sequentially) was shown to increase effectiveness in normalizing cortisol levels.2

In an interview with EndocrineWeb, Eliza B. Geer, MD, medical director of the Multidisciplinary Pituitary and Skull Base Tumor Center at Memorial Sloan Kettering Cancer Center in New York City, noted that most medical therapies for Cushing’s syndrome are used off-label (in the US), and thus may lack clinical trial efficacy and safety data; consequently, this review provides useful information for treatment selection. However, Dr. Geer said there was substantial diversity of treatments reviewed in this paper – including tumor-directed therapies, cortisol synthesis inhibitors, an adrenolytic therapy, and a receptor blocker, used alone or in combination.

Further, treatments used in the studies addressed a range of Cushing’s etiologies and reflected heterogeneous study designs (for example follow-up ranged from 2 weeks to 11.5 years).2  As such, she said, “findings provided by this review should be viewed in the context of a broader clinical understanding of Cushing’s treatment.”

Specifically, Dr. Geer said, “Dr. Broersen’s analysis found that efficacy of medical therapy was improved by prior radiotherapy. But we know that radiotherapy is recommended on an individualized basis in only a fraction of Cushing’s patients, depending on tumor behavior and treatment history. Also, the fact that mitotane was shown here to have the highest efficacy of all therapies does not make this the appropriate treatment for all, or even most, Cushing’s patients; mitotane is adrenolytic and has a high rate of significant adverse effects.”

Too Many Questions Persist, Necessitating Focus on Attaining Management Paradigm

Dr. Geer also highlighted the need for answers to basic questions when investigating Cushing’s treatments: How do we define ‘successful’ treatment? What goals of care can patients expect? Which cortisol measurements and cut-offs can be used? How do we define clinical remission—resolution of which symptoms and comorbidities? She said Cushing’s syndrome is one of the most challenging endocrine diseases to treat because of the lack of an accepted, universal treatment or management paradigm.

Treatment is often multimodal and always multidisciplinary, with patient-specific decision trees that must consider many factors, including goals of care, treatment history, disease etiology and severity, tumor behavior, and individual responses to medical therapies, she told EndocrineWeb.

She concluded, “While Broersen et al’s study provides a useful review of available medical therapies, it reinforces something we already know about the treatment of Cushing’s: Expertise is required.”

Pituitary surgery is first-line treatment for Cushing’s disease. Currently, there are two main techniques for transsphenoidal pituitary surgery: microscopic and endoscopic. The operating microscope provides three-dimensional vision and may be advantageous in identifying small tumors; the broader field of vision afforded by the endoscope may be advantageous for complete resection of large tumors.3  Generally, despite an absence of studies directly comparing relative remission and complication rates between microscopic versus endoscopic approaches, most surgical centers choose to use one or the other; few have both.3

Examining the Surgical Options to Manage Cushing’s Disease

The second systematic review is the first to compare remission and recurrence rates, and mortality after microscopic versus endoscopic transsphenoidal pituitary surgery for Cushing’s disease.3 The review included 97 studies of 6695 patients: 5711 individuals having the microscopic procedure and 984 undergoing endoscopic surgery.

Results of the meta-analysis found no clear difference between the two techniques in overall remission (80%) or recurrence (10%).3 Short-term mortality for both techniques was < 0.5%. However, endoscopic surgery was associated with a greater occurrence of cerebrospinal fluid leak (12.9 vs 4.0%) but a lesser occurrence of transient diabetes insipidus (11.3 vs 21.7%).3

The authors reported a higher percentage of patients in remission (76.3 vs. 59.9%) and lower percentage recurrence rates (1.5 vs 17.0%) among patients undergoing endoscopic surgery for macroadenomas.3

When interviewed regarding the second meta-analysis,3 Dr. Geer said that the potential benefit of endoscopy over microscopy has been questioned for ACTH-secreting tumors specifically since most are microadenomas.

“With the caveat that few studies (four of the 97 reviewed) compared techniques directly, Broersen et al3 found that endoscopic surgery was associated with higher remission rates compared to microscopic surgery for large tumors, but the two techniques were comparable for small tumors,” said Dr. Geer, however, “one limitation of these data is the lack of standardized criteria to define diagnosis and remission of Cushing’s among the studies reviewed.”

Need for Consistency in Clinical Trials and Surgical Expertise

The study investigators concluded, “endoscopic surgery for patients with Cushing’s disease reaches comparable results for microadenomas, and probably better results for macroadenomas than microscopic surgery,” despite the greater learning curve associated with endoscopic surgery.3 As such, based on their findings, the authors concluded that “endoscopic surgery may thus be considered the current standard of care. Microscopic surgery can be used based on neurosurgeon’s preference.” They did not respond to EndocrineWeb for a request for comment.

As more neurosurgeons receiving training with the endoscope, the preferred technique for pituitary surgery is changing. Dr. Geer said, “Broersen’s review provides reassurance that the newer endoscopic technique is at least equal to the microscope for microadenomas and may be preferred for macroadenomas.”

“However, [conclusions based on the systematic review] do not change our role as endocrinologists treating Cushing’s disease, which is to refer, when indicated, to the available neurosurgeon with the most favorable outcomes and lowest rate of complications, both of which depend directly on level of experience with the procedure and the instrument being used, whether endoscope or microscope,” she said.

The authors had no financial conflicts to declare.

From https://www.endocrineweb.com/professional/cushings/cushings-syndrome-eludes-treatment-paradigm-standard-approach-care

Cushing’s syndrome caused by ACTH-producing thymic typical carcinoid with local invasion and regional lymph node metastasis: a case report

  • Wakako Fujiwara Email author View ORCID ID profile,
  • Tomohiro Haruki,
  • Yoshiteru Kidokoro,
  • Takashi Ohno,
  • Yohei Yurugi,
  • Ken Miwa,
  • Yuji Taniguchi and
  • Hiroshige Nakamura
Surgical Case Reports20184:55

https://doi.org/10.1186/s40792-018-0459-7

Received: 28 March 2018

Accepted: 31 May 2018

Published: 11 June 2018

Abstract

Background

Ectopic ACTH-producing thymic carcinoid tumors are rare, but often behave aggressively with local invasion and distant metastasis. We herein report a case of ACTH-producing thymic typical carcinoid tumor with lymph node metastasis treated by surgery and postoperative radiation therapy.

Case presentation

A 61-year-old woman was admitted to be evaluated for hypoglycemia and hypokalemia. Laboratory data revealed elevation of serum cortisol and ACTH levels. Overnight administration of 8 mg dexamethasone did not suppress plasma ACTH. Chest CT demonstrated a tumor of 30 mm in diameter and enlargement of the lymph node at the anterior mediastinum. Ectopic ACTH syndrome was suspected and total thymectomy and lymph node dissection were performed. The histopathological examination indicated typical carcinoid tumor and mediastinal lymph node metastasis, and immunohistochemical staining was positive for ACTH. The plasma ACTH level decreased immediately after surgery. She received postoperative radiation therapy of 60 Gy.

Conclusion

Ectopic ACTH-producing thymic typical carcinoid tumors are rare, and it is important to consider this disease and perform appropriate treatment.

Keywords

Thymic carcinoid ACTH Cushing’s syndrome Total thymectomy

Background

Among adrenocorticotrophic hormone (ACTH)-dependent Cushing’s syndrome, 10–20% is due to nonpituitary tumors termed ectopic ACTH syndrome (EAS). The most common cause of EAS is small cell lung cancer, followed by thymic carcinoids. Thymic carcinoids are very rare neuroendocrine tumors that often complicate endocrine disorders. Although previously assumed to be variants of bronchopulmonary carcinoid tumors, they are generally more aggressive and difficult to treat. It is widely accepted that surgical resection is the only curative treatment for localized lesions, and the efficacy of chemotherapy and radiotherapy has not been well established.

We herein report a case of EAS caused due to a thymic typical carcinoid tumor successfully treated by surgery followed by radiation.

Case presentation

A 61-year-old woman visited her primary care doctor because of general malaise, face edema, skin pigmentation, insomnia, and polyuria. Blood examination revealed marked hypokalemia and impaired glucose tolerance. Bilateral adrenal enlargement was observed on abdominal ultrasonography, and she was referred to our hospital for further examination. Endocrine examination showed both elevated plasma cortisol (107.7 pg/mL) and ACTH levels (1100 pg/mL), and increased urinary excretion of free cortisol (6650 mcg/day) and 17-ketogenic steroids (78.7 mg/day). Plasma cortisol and ACTH levels were elevated without any diurnal rhythm. Plasma cortisol was not suppressed by the overnight 8-mg dexamethasone suppression test. There was no response of plasma ACTH or cortisol to exogenous corticotropin-releasing hormone (CRH). Other hormones of the pituitary, thyroid, and adrenal medulla were all in normal ranges. Thus, ectopic ACTH syndrome was strongly suggested.

Chest computed tomography (CT) demonstrated a tumor of approximately 30 mm in diameter and enlargement of the lymph node in the anterior mediastinum (Fig. 1). High accumulation of 18-fluorodeoxyglucose in the anterior mediastinum tumor (maximum standardized uptake value [SUV] 2.48) but not in the lymph node was observed on positron emission tomography (PET)/CT. Somatostatin receptor scintigraphy also revealed mild uptake in the tumor. Collectively, these data were consistent with a diagnosis of EAS caused by an anterior mediastinum tumor, possibly thymic carcinoid tumor. There was no abnormal finding indicating multiple endocrine neoplasia (MEN).

Figure 1
Fig. 1

Chest CT image. A tumor (30 × 30 × 14 mm) without invasion localized in the anterior mediastinum (a). Enlargement of lymph node (b)

Before the operation, we administered 500 mg/day of metyrapone, and both ACTH and cortisol levels decreased to 68.5 pg/mL and 3.02 mcg/mL respectively. After 2 months of medical treatment, her symptoms were relieved and bilateral adrenal enlargement decreased. Under open thoracotomy by median sternotomy, she underwent total thymectomy, pericardial partial resection, dissection of the anterior regional and the right paratracheal lymph nodes, and sampling of the subcarinal lymph node. Histopathologically, the tumor consisted of round to spindle-shaped cells with high nucleus/cytoplasm ratios containing finely granular chromatin. Necrosis was absent, and mitotic figures were infrequent, with less than two per ten high-power fields (HPF). Tumor cells were positive for chromogranin A, synaptophysin, CD-56, and ACTH on immunohistochemistry (Fig. 2). The tumor had invaded the pericardium, and mediastinal lymph nodes were positive for metastasis. The final diagnosis was stage IVA (pT2N1M0) ACTH-producing thymic typical carcinoid tumor. The plasma ACTH level decreased to 14.8 pg/mL, less than normal, immediately after surgery (Fig. 3). Hydrocortisone was administered during the perioperative period and was gradually tapered, and finished 4 months after surgery. She received postoperative radiation therapy of 60 Gy. At 8 months after surgery, she showed no sign of Cushing’s syndrome or recurrence of the tumor without any medications.

Figure 2
Fig. 2

HE staining (a) indicated typical carcinoid tumor. Tumor cells were positive for synaptophysin (b), CD-56 (c), and ACTH (d) on immunostaining

Figure 3
Fig. 3

Changes in plasma ACTH levels during the clinical course

Discussion

Ectopic ACTH-producing thymic carcinoid tumor is an extremely rare clinical condition, comprising 29% of all thymic carcinoids and 5–42% of all ectopic ACTH-producing syndrome [12]. It has been reported that radical surgical resection of the ACTH source is the only effective treatment [3]. Prior to surgery, medication therapy should be done to prevent perioperative complications and perform surgery when hormone values and symptoms are controlled. Furthermore, there is a risk of postoperative adrenal insufficiency; strict perioperative management is desirable.

Unlike pulmonary and other carcinoid tumors, thymic carcinoids often behave aggressively as an advanced disease with local invasion, lymph node metastasis, and distant metastasis because of the high proportion of atypical carcinoid tumors. Regarding ACTH-producing thymic tumors, Neary et al. reported three cases of well-differentiated ACTH-producing thymic neuroendocrine carcinomas, and the patients had no lymph node metastasis, recurrence, or death. On the other hand, nine cases of moderately differentiated ACTH-producing thymic neuroendocrine carcinomas almost had lymph node metastasis, and all patients had recurred [4]. However, our case was a typical carcinoid tumor with lymph node metastasis and local invasion.

As a surgical procedure, a median sternotomy approach is generally recommended because this enables excision of the entire thymus, perithymic fat, other affected mediastinal structure, and aggressive lymph node dissection. However, there is no standard for lymph node dissection in thymic epithelial tumors even though lymph node metastasis is an important prognostic factor. Hwang et al. recommended right paratracheal node dissection in addition to anterior regional lymph node dissection for TNM clinical stage II or higher diseases because they are crucial stations on the lymphatic pathway of thymic malignancies [5]. In the present case, we performed total thymectomy, followed by lymph node dissection of the anterior regional and right paratracheal nodes, and sampling of subcarinal lymph node via median sternotomy. The anterior mediastinal lymph nodes were positive for metastasis. Consequently, we considered the extent of lymph node dissection to be adequate, and radical resection was completed because the postoperative plasma ACTH level was successfully decreased. Although a good prognosis is expected by combined surgery and radiation, relatively high malignancy characteristics are observed compared with typical carcinoids, and strict follow-up is needed.

Conclusion

We report a rare case of ectopic ACTH-producing thymic typical carcinoid with local invasion and regional lymph node metastasis. Surgical resection was effective to control Cushing’s syndrome in this case, and nodal staging may help to guide adjuvant treatment, but systemic nodal dissection/sampling is yet to be standardized.

Abbreviations

ACTH: 

Adrenocorticotrophic hormone

CRH: 

Corticotropin-releasing hormone

CT: 

Computed tomography

SUV: 

Standardized uptake value

PET: 

Positron emission tomography

MEN: 

Multiple endocrine neoplasia

HPF: 

High-power fields

CD-56: 

Cluster of differentiation-56

Declarations

Acknowledgements

The authors thank Dr. Nosaka and Dr. Umekita for diagnostic assessment of this case.

Availability of data and materials

The dataset supporting the conclusions of this article is included within the article.

Authors’ contributions

WF and YT were the attending doctors for the patient. WF, YK, KM, YT, and HN performed the operation. WF, TH, and HN drafted this manuscript. All authors have read and approved the final manuscript.

Ethics approval and consent to participate

No applicable.

Consent for publication

This patient consented to the reporting of this case in a scientific publication.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

References

  1. Yoshikawa T, Noguchi Y, Matsukawa H, et al. Thymus carcinoid producing parathyroid hormone (PTH)-related protein: report of a case. Surg Today. 1994;24:544–7.View ArticlePubMedGoogle Scholar
  2. Alexandraki KI, Grossman AB. The ectopic ACTH syndrome. Rev Endocr Metab Disord. 2010;11:117–26.View ArticlePubMedGoogle Scholar
  3. Zhou X, Hnag J, Che J, et al. Surgical treatment of ectopic adrenocorticotropic hormone syndrome with intra-thoracic tumor. J Thorac Dis. 2016;8:888–93.View ArticlePubMedPubMed CentralGoogle Scholar
  4. Neary NM, Lopez-Chavez A, Abel BS, et al. Neuroendocrine ACTH-producing tumor of the thymus—experience with 12 patients over 25 years. J Clin Endocrinol Metab. 2012;97:2223–30.View ArticlePubMedPubMed CentralGoogle Scholar
  5. Hwang Y, Park IK, Park S, et al. Lymph node dissection in thymic malignancies: implication of the ITMIG lymph node map, TNM stage classification, and recommendations. J Thorac Oncol. 2016;11:108–14.View ArticlePubMedGoogle Scholar

Copyright

© The Author(s). 2018

Etomidate Found Effective in Severe Cushing’s Syndrome

Etomidate — a steroid synthesis blocker — is an effective treatment for patients with severe Cushing’s syndrome who do not respond to ketoconazole, according to a new case report from Mexico.

The report, “Etomidate in the control of severe Cushing’s syndrome by neuroendocrine carcinoma,” appeared in the journal Clinical Case Reports.

The investigators reported the case of a 51-year-old woman with ectopic Cushing’s syndrome caused by a pancreatic tumor. Ectopic Cushing’s refers to cases of excess secretion of adrenocorticotropin hormone (ACTH) outside the pituitary or adrenal glands.

The patient underwent distal pancreatectomy — the surgical removal of the bottom half of the pancreas — in 2015 due to an ACTH-secreting tumor. Although she had a good initial response, liver metastasis was evident by 2016.

Compared to measurements in 2016, morning blood cortisol, 24-hour urinary-free cortisol, and ACTH levels significantly increased in 2017. The patient also showed low levels of the luteinizing and follicle-stimulating hormones, which the scientists attributed to her severe hypercortisolism (excess cortisol levels).

The woman was being treated with ketoconazole to lower her cortisol values and later received chemoembolization — a method to reduce blood supply and deliver chemotherapy directly to a tumor — for her liver metastasis.

Although ketoconazole is generally the treatment of choice for the control of hormone production in the adrenal glands, its effectiveness is often limited and is associated with side effects, clinicians noted.

In April 2017, the patient arrived at the emergency room with sepsis — a potentially life-threatening complication of an infection — that originated in the gut.

Because ketoconazole had failed to lower cortisol levels, the patient started receiving infused etomidate, an inhibitor of the enzyme 11‐beta‐hydroxylase that prevents cortisol synthesis.

This treatment was stopped one day before the bilateral removal of the adrenal glands as a definitive treatment for the elevated production of cortisol.

While the patient experienced decreased levels of potassium, calcium, and magnesium with an initial dose of 0.04 mg per kg body weight an hour of etomidate, a gradual decrease of etomidate — depending on her cortisol levels — corrected these alterations.

After surgery, the patient showed a significant improvement in her general health, including control of her sepsis. She is currently taking hydrocortisone and fludrocortisone, with treatment for liver metastasis pending.

“Etomidate is a very effective drug in severe Cushing’s syndrome that is refractory to ketoconazole,” the researchers wrote.

“Control of the serum cortisol levels in ectopic Cushing’s syndrome can be obtained with infusion rates much lower than those used in anesthesia, without respiratory side effects,” they added.

The authors recommend an initial dose of etomidate of 0.04 mg/kg per hour, daily monitoring of 24-hour urinary cortisol and cortisol levels, and a gradual decrease of the etomidate dose according to daily measurements of metabolites.

From https://cushingsdiseasenews.com/2018/05/17/severe-cushings-syndrome-case-study-finds-etomidate-effective-therapy/

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