Adrenal

Right adrenal tumors are frequently missed

Right adrenal tumors are frequently missed

A serious article analyzing the prevalence of left-sided vs. right-sided adrenal tumors. Prior observations have consistently shown that left-sided adenomas are more common than right-sided ones, in 2:1 ratio.

Although a reason could be embryological, leading to a greater left adrenal vascularity, innervation, volume and mass; authors suggest that asymmetry could also be due to anatomical locations of the glands.

The left adrenal gland is surrounded by the hypo-attenuated visceral fat, making it easier to be seen by imaging, versus the right gland which is somewhat compressed by the relatively hyper-attenuated liver and kidney.

Authors' argument is compelling enough that clinicians should be aware of possibly missing right-sided adrenal tumors, especially in the context of hyper-functionality; elevated catecholamines, cortisol, aldosterone and DHEAs.

GT

Late-night salivary cortisol measurements are not consistent in cushing disease

Late-night salivary cortisol measurements are not consistent in cushing disease

The study reveals that late-night salivary cortisol (LNSC) measures are variable in cushing disease, particularly in those with recurrent or persistent illness. Less variability was seen in new cases of the disease who had not undergone treatment. Hypercortisolemia is expected to be lower in treated vs. untreated patients, thus it is reasonable to suspect similar inconsistencies in LNSC values in those with subtle hypercortisolemia, frequently seen with adrenal adenomas.

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A rare source of cushing's syndrome: ovary

A rare source of cushing's syndrome: ovary

Cushing's syndrome (CS) is a rare illness that leads to visceral adiposity, muscle wasting, insulin resistance, osteoporosis, diabetes, blood clots, high blood pressure, dyslipidemia and frequent infections. Subsequently, affected individuals have increased mortality rates.

The most common cause of the syndrome is a pituitary tumor, otherwise called cushing disease. Although rare, other organs also have the potential of producing excessive cortisol. The article describes a unique case of CS where the source is a right ovarian mass. The selective ovarian and adrenal venous sampling was important in confirming the diagnosis, and eventually driving the therapy.

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How to supplement the real adrenal fatigue

How to supplement the real adrenal fatigue

Results of the article suggest that longer-acting cortisol-equivalent supplementation is more beneficial than conventional therapy with multiple daily doses of hydrocortisone in adults with adrenal insufficiency.  Advantages are reduced body weight, heightened immunity, less recurrent infections, and improved quality of life. A group of 89 participants were followed for 6 months.

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Adrenal hormones are useful in sepsis

Adrenal hormones are useful in sepsis

This is a major trial evaluating the usefulness of hydrocortisone and fludrocortisone during septic shock. About 12,000 patients were followed for 30-120 days. Compared to placebo, high doses of adrenal hormone equivalents improved 90-day death rates significantly. This is a step forward in improving the care of the deadly condition.

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Pituitary disorders caused by cancer immunotherapy

Pituitary disorders caused by cancer immunotherapy

Cancer immunotherapy is becoming more common due to its specificity and efficacy. However endocrinopathy is an undesirable byproduct. Ipilimumab, approved for melanoma, has shown to cause pituitary anomalies in 10-15% of patients.

Current report reveals two cases of hypophysitis caused by a different immunotheraputic agent, atezolizumab. Unlike Ipilimumab, atezolizumab seems to have a higher inclination for corticotroph destruction leading to late-onset central adrenal insufficiency. 

It is important to be aware of endocrine disorders associated with cancer immunotherapy as early diagnosed and management could be life saving.

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The other aldosterone blocker, eplerenone, helps with hypertension

The other aldosterone blocker, eplerenone, helps with hypertension

The aim of this review was to determine the effectiveness of eplerenone for reducing blood pressure, its side effect profile, and its impact on clinically meaningful outcomes such as mortality and morbidity.

Clinicians have used eplerenone to treat high blood pressure since 2002. It is important to determine the clinical impact of all antihypertensive medications used in patients to support their continued use in essential hypertension.

The eplerenone dose ranged from 25-400 mg daily. Patients were followed for 8-16 weeks while on therapy. There is currently no evidence that eplerenone has a beneficial effect on life expectancy or complications related to hypertension.

The study finds that eplerenone 50-200 mg/day reduces systolic BP by approximately 9 mmHg and diastolic BP by 4 mmHg compared to taking no medication.

CDSR

Aldosterone vs. renin, a cardiometabolic cat-and-mouse game

Aldosterone vs. renin, a cardiometabolic cat-and-mouse game

Study results are important from several aspects. It confirms prior findings that excess aldosterone increases cardiometabolic sequelae, like cardiovascular events, diabetes, atrial fibrillation and mortality, independent of high blood pressure.

More importantly the study guides us on how to objectively reduce the above risks: the dose of mineralocorticoid receptor antagonists, such as spironolactone or eplerenone, could be adjusted to achieve higher plasma renin activity of ≥1 μg/L/hr.

Plasma renin activity is clinically available and a good biochemical measure of hyperaldosterone end-product, as shown in the figure below.

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Adrenal-diabetes connection

Adrenal-diabetes connection

Diabetes and prediabetes are the most common endocrine conditions affecting about 38% of the US population. Adrenal tumors on the other hand are relatively rare with prevalence of < 10%. Results of the article suggest that adrenal tumors, even when "benign" or "nonfunctional", can contribute to the development of diabetes and prediabetes.

Apparently "benign" adrenal masses could be an independent risk factor for glucose dysmetabolism. Should patients with diabetes be screened for such tumors? If present, would surgical or medical intervention reduce this risk?

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Primary hyperaldosteronism amplifies cardio-metabolic anomalies

Primary hyperaldosteronism amplifies cardio-metabolic anomalies

Important to diagnose primary hyperaldosteronism early as a cause of high blood pressure since patients are even at a higher risk for: stroke, coronary artery disease, atrial fibrillation, heart failure, left ventricular hypertrophy, diabetes and metabolic syndrome.

Risks were evenly high for both aldosterone-producing adenoma and bilateral adrenal hyperplasia. About 13,000 patients were followed for 9 years.

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More options for Cushing's disease

More options for Cushing's disease

Cushing's disease is a rare debilitating endocrine disorder for which few prospective interventional studies have been done. Long-acting pasireotide normalised mean urinary free cortisol concentration in about 40% of patients with Cushing's disease at month 7 and had a similar safety profile to that of twice-daily subcutaneous pasireotide.

Long-acting pasireotide is an efficacious treatment option for some patients with Cushing's disease who have persistent or recurrent disease after initial surgery or are not surgical candidates, and provides a convenient monthly administration schedule.

Lancet

Obstructive sleep apnea in cushing's syndrome

Obstructive sleep apnea in cushing's syndrome

Cushing's syndrome is a rare endocrine illness. Although its reported  incidence is about 10 cases per million people each year, it is estimated to be much higher in subclinical scenarios. It can lead to several pathologies such as diabetes, hypertension, high triglycerides, blood clots, osteoporosis, muscle loss and cardiovascular mortality.

The current study adds obstructive sleep apnea as another possible complication of CS, independent of age, gender, body mass index and insulin resistance.

Should patients with obstructive sleep apnea be screened for subclinical cushing’s syndrome?

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Prolactinoma, pheochromocytoma and MAX gene

Prolactinoma, pheochromocytoma and MAX gene

Pheochromocytomas are rare neuroendocrine tumors. They could be adrenal vs. extra-adrenal, sporadic vs. familial, isolated vs. multifocal, or benign vs. malignant. MAX gene mutation has recently been recognized as an unusual cause of familial pheochromocytoma.

This article documents the first patient with simultaneous germline MAX mutation, pituitary prolactinoma, bilateral pheochromocytoma and mild primary hyperparathyroidism.

Could the germline MAX mutation be a direct cause of prolactinoma as well?

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Laboratory interference gives false results on various hormone measures

Laboratory interference gives false results on various hormone measures

An important case pointing to the endocrinologist's dilemma when facing inappropriate or discordant hormonal results. This patient had severely high levels of serum estradiol, progesterone, testosterone, and cortisol in complete absence of clinical signs and symptoms.

Mass spectrometry, an expensive and poorly available analytical technique, saved the day. Mild monoclonal IgG elevation (hypergammaglobulinemia) was felt to be the interfering agent leading to falsely high hormone measures. Interference could also occur in the setting of heterophilic antibodies, rheumatoid factor and biotin intake, none which were present in this case.

Important to be aware of false deviations in blood work, as inability to realize it could generate unnecessary anxiety, testing, imaging, procedures and even intervention.

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Atypical adrenal mass

Atypical adrenal mass

Roughly 90% of congenital adrenal hyperplasia is categorized as "classical" due to full (70%, cortisol and aldosterone, salt-wasting) or partial (30%, cortisol alone, simple virilizing) deficiency of 21-hydroxylase. Scant or nonfunctioning 21-hydroxylase reduces cortisol synthesis. Lower background cortisol causes persistent ACTH rise, which stimulates chronic adrenal hyperplasia.

This patient case uncovers that constant ACTH stimulation, besides hyperplasia, can also lead to a functional adrenal mass; characterized as a lipid rich structure (myelolipoma) with increased uptake on 18F-FDG PET scan. Alike masses are seen in testicular glands (called testicular adrenal-rest tumorsof male patients with classical congenital adrenal hyperplasia.

Important to be aware of functional myelolipomas as they do not represent a malignant process.

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Diabetes & high cortisol

Diabetes & high cortisol

Diabetes is prevalent, estimated to affect 10% of population. Cushing's syndrome (CS) on the other hand is rare, 2–3 cases/million per year. Clinical manifestations of diabetes and early CS are similar; increased glucose, blood pressure, cholesterol and abdominal circumference.

Authors find that subtle cortisol elevation is present in 3.5% of persons with type 2 diabetes, with the main source being adrenal adenomas. It is reasonable to screen DM2 patients with "cushing's syndrome" features, as surgical cure is a possibility.

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Pheochromocytoma & its effect on carotids and heart

Pheochromocytoma & its effect on carotids and heart

Adrenal medulla is responsible for production of catecholamines, mainly epinephrine and nor-epinephrine. Catecholamines are physiologically important as they contribute to the sympathetic nervous system. 

Excessive production of epinephrine and nor-epinephrine leads to pheochromocytoma, which can manifest clinically as severe hypertension, increased heart rate, excessive sweating, flushing, headaches and even anxiety.

This article shows that successful removal of the cause of pheochromocytoma reverses abnormal thickening of carotid arteries and heart muscles; adding value to good longer-term prognosis.

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Aldosterone & Vertebral Fractures

Aldosterone & Vertebral Fractures

Elevated autonomous aldosterone production is more common than previously believed. Primary aldosteronism is estimated to cause "essential" and resistant hypertension in up to 10% and 20% of adults. These numbers are significant given wide prevalence of high blood pressure in the general population.

This original study suggests that primary aldosteronism is also a unique contributor to vertebral fracture, raising its risk by 3 fold. Authors hypothesize that excessive aldosterone causes fracture by reducing bone quality rather than bone density. A partial effect could also be its ability to increase urinary calcium excretion in the distal tubule.

Important to note the association of hyperaldosteronism with metabolic syndrome, higher A1c and Triglycerides and lower HDL.

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Subclinical hypercortisolism & DHEAs

Subclinical hypercortisolism & DHEAs

Cortisol, produced by adrenal glands, is central to human physiology. It helps maintain proper blood pressure, glucose metabolism and electrolyte homeostasis, among other processes. Its direct involvement is also seen in the fight or flight response.

However when abnormally high, it can lead to detrimental health issues, best summarized in Cushing’s syndrome. Although Cushing’s syndrome is rare, subtle cortisol elevations are not. Recent research indicates that slight to moderate rise in cortisol could also lead to weight gain, diabetes, hypertension and bone fractures.

Currently the gold standard measure for subtle hypercortisolism is overnight low dose dexamethasone suppression test due to high sensitivity >99%. This original article identifies serum DHEAs as a better test due to the same sensitivity but improved specificity. The study was done in patients with adrenal mass of unknown significance, more properly termed adrenal incidentalomas.

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2016 Endocrine Society Guidelines: CENTRAL Adrenal Insufficiency

2016 Endocrine Society Guidelines: CENTRAL Adrenal Insufficiency

Adrenal Insufficiency (AI) is defined by low cortisol production.  It could be due to failure, infection, injury, bleeding or inflammation of the adrenal glands, or from limited production of ACTH hormone by the pituitary.  

Adrenal Insufficiency as a result of low ACTH is called “central” or “secondary”. These guidelines were developed by Endocrine Society to address specifically Central AI. They were released in November 2016.

Please find below excerpts with slightly modified wording for easier and succinct reading.

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