E-Poster Presentation 63rd Endocrine Society of Australia Annual Scientific Meeting 2020

A 45 year old man, with 2 children, known to have depression and anxiety presented with a 2 year history of fatigue and lethargy and a recent history of loss of libido and a decreased need to shave. There was no associated visual disturbance or headaches and no complaints suggestive of a systemic aetiology for his symptoms, and no polydipsia/polyuria. Other than a history of previous heroin dependence some years before, there was no history of current illicit substance use. He had been taking various opioids and analgesia for some time for relief of back pain. 

His clinical examination revealed bilateral gynaecomastia, sparse body hair, but normal testicular volume. Visual fields were intact. BMI 35kg/m2, BP 129/81 mmHg(lying), 115/75mmHg (standing).

Breast ultrasound confirmed gynaecomastia L>R.. Beta HCG was normal and oestradiol was low. Bioochemistry revealed profound hypogonadism, hypocortisolaemia, low serum TSH with low-normal fT4 suggestive of secondary hypothyroidism. Iron studies, angiotensin converting enzyme, copper and calcium were normal.

An MRI of the pituitary and stalk was normal.

He required anterior pituitary hormone replacement with hydrocortisone, thyroxine and testosterone, which resulted in clinical improvement. As he gradually came off opioid medications over the next 10 months, his pituitary axis recovered fully. He was able to cease hydrocortisone, thyroxine and testosterone, and he remains well.

This case illustrates the need to consider rarer and unusual aetiologies of hypothalamic-pituitary axis (HPA) suppression that may be reversable. Many drugs affect the HPA, but usually do not affect all anterior hormones simultaneously.

The pulsatility and secretion of GnRH is under the control of many neuro-hormonal mechanisms, which include various neurotransmitters, endogenous opioids and steroid hormones. It has long been recognised that exogenous opioids exert various effects on this axis, either by inhibiting the release of GnRH, or by decreasing the responsiveness of FSH to negative feedback from sex steroids. The resultant effect is that LH is lower and sex steroids are suppressed, but FSH levels are only minimally affected. In addition to this effect, testosterone is under the control of LH, which too, is suppressed by exogenous opioids. This complex interaction of opioids causes overwhelming hypogonadism. (1)

The cortisol endocrinopathy associated with chronic opioid use, is more complex , as studies have indicated suppression of the cortisol axis with sustained oral morphine doses of 30-240mg /day, makes it likely that many people may be affected by chronic opioid use and under-recognized by clinicians. Still, not everyone with a low serum ACTH and cortisol level will need steroid replacement as stimulation studies have previously shown that the cortisol axis, although abnormal at baseline, may still be intact.(3) 

Hyperprolactinaemia, not demonstrated in our case, is also a recognised consequence of opioid use despite the poorly understood mechanisms for this; however, this may have additional effects on hypogonadism and bone health. Opioids have a complex effect on the growth hormone axis in humans - the net effect is mild stimulation of GH release.(4)

Different opioids have shown different effects on thyroid hormone levels, the mechanism may be due to alterations in thyroid binding globulin, rather than direct effect on the HPA axis (5). Irrespective of this, clinically significant thyroid dysfunction is unusual.(5)

In summary, opioid suppression of the HPA can be a diagnostic challenge. This case illustrates opioid-induced hypopituitarism necessitating the need for anterior hormone replacement temporarily and alerts the clinician to the complex interplay of opioids on the HPA axis and the possible reversibility of the condition.

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