What Is Homeostasis?

Homeostasis is the body’s ability to adapt continuously — in order to maintain stable internal conditions despite external environmental shifts. At the heart of this intricate regulatory system lies the endocrine feedback loop — the foundational mechanism by which the body achieves and sustains homeostasis.

What is the Endocrine Feedback Loop?

As an endocrinologist, a clear understanding of endocrine feedback loops is paramount. These loops play a vital role in visualizing the endocrine system and, more importantly, in practicing endocrinology correctly.

New FDA approval: oral medication for Cushing’s disease

Cushing’s syndrome (CS) is a rare condition. It’s health consequences can be severe, leading to visceral adiposity, muscle weakness, depression, insulin resistance, diabetes, blood clots, reduced immune system, and cardiovascular disease.

A portion of patients diagnosed with CS has Cushing’s disease (CD). In Cushing’s disease, the root cause of hypercortisolism is a pituitary tumor producing excessive ACTH hormone. The preferred treatment is pituitary surgery. Unfortunately, in a small subset of patients, the operation is not successful or indicated.

To address the health concerns for individuals who are not responsive or candidates for pituitary tumor resection, the FDA has now approved a backup treatment via the oral drug Isturisa.

Isturisa, taken twice daily, is a potent inhibitor of 11-β-hydroxylase, a key enzyme in cortisol production. Side effects can include relative adrenal insufficiency, swelling, nausea, vomiting, and headaches. Clinical studies have shown that about 50% of patients respond to therapy.

Isturisa is an excellent addition to the arsenal of combating refractory Cushing’s disease.

Dr. Tashko

Levoketoconazole therapy for Cushing’s syndrome

Cushing’s syndrome is defined by a persistent or cyclical increase in blood cortisol concentrations. The professional diagnosis is based on two or more positive tests: low dose dexamethasone suppression, late-night salivary cortisol, or 24-hour urinary free cortisol.

Surgery is the treatment of choice, which often leads to a permanent cure. However, not infrequently, the source of hypercortisolism cannot be identified, or surgical intervention is not sufficient. In such circumstances, medical therapy is preferred over watchful waiting.

SONICS was a phase 3, open-label, non-randomized clinical trial. Its investigators tested the utility of levoketoconazole in normalizing urinary cortisol levels in 94 adults with uncontrolled Cushing’s syndrome.

After full dose titration and 6-month maintenance therapy, about 30% of patients achieved the desired outcome, as defined by normalized urinary cortisol concentrations. The rate of adverse events was not insignificant: nausea 32%, headaches 28%, study discontinuation 13%, and increased liver enzyme in 11% of participants.

Although the study results are not stupendous, they are meaningful and provide additional options for patients with refractory or uncontrolled Cushing’s syndrome.


Incidence of Cushing’s disease is on the rise

The study finds that the incidence of pituitary Cushing is still rare but increased over the past 30 years. Its current incidence is estimated to be 2.0 cases/million/year. However it is unknown if this increase is real or due to improved physician awareness and biochemical testing.


Pituitary enlargement due to hypothyroidism

Another nice report of total pituitary enlargement due to the long-standing untreated primary hypothyroidism. Low levels of FT3 and FT4 lead to excessive TRH and TSH production, in turn causing pituitary expansion.

This case is unique as it is found in a child suffering from growth retardation. Proper treatment with thyroid hormone supplementation reversed the illness.


Prolactin Resistance

This is a nice case of prolactin resistance due to loss-of-function variant in the prolactin receptor (PRL-R) gene. A 35 year old female with hyperprolactinemia became pregnant twice, but was unable to lactate. It would take some time before the PRL-R genetic testing becomes available in clinical practice. Nonetheless, the case expands our knowledge of prolactin pathogenesis.


2018 Testosterone Therapy Guidelines

This is an update of previous guidelines published in 2010.

We recommend T therapy for men with symptomatic T deficiency to induce and maintain secondary sex characteristics and correct symptoms of hypogonadism after discussing the potential benefits and risks of therapy and involving the patient in decision making. 

We suggest that when clinicians institute T therapy, they aim at achieving T concentrations in the mid-normal range during treatment with any of the approved formulations.

Clinicians should monitor men receiving T therapy using a standardized plan that includes: evaluating symptoms, adverse effects, and compliance; measuring serum T and hematocrit concentrations; and evaluating prostate cancer risk during the first year after initiating T therapy.


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.


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.


New FDA approval: a more convenient test for adult growth hormone deficiency

FDA has approved the oral agent macrilen for evaluation of growth hormone deficiency in adults. Macrilen is a ghrelin agonist which leads to the provocative release of growth hormone by the anterior pituitary gland. The diagnostic procedure is safe, efficient and comparable with the gold standard isulin tolerance test (ITT). This is a meaningful advancement in the field of endocrinology.