Endocrine Abstracts

Case Report: A 25-year-old man presented in 2018 with 3-year history of severe hypogonadism symptoms (fatigue, difficulty concentrating, low libido and mood). His initial investigations indicated hypogonadotropic hypogonadism (HH): virtually undetectable serum testosterone (1.4 nmol/l) with inappropriately low gonadotrophins (FSH 1.4 IU/l, LH 2.0 IU/l). The serum prolactin level and the rest of the pituitary profile were in the normal ranges; while a pituitary MRI scan was also reported as normal. He had well developed secondary sexual characteristics. His haemoglobin was 121 g/l (130-170) with low haematocrit, consistent with the effect of androgen deficiency on haemopoiesis, while osteopenia was reported on a bone-density scan. He responded impressively to testosterone replacement therapy. 18 months later, he developed arthralgia, prompting further investigation. He was found to have a markedly elevated serum ferritin of 3,957 µg/l. Genetic testing confirmed a homozygous HFE gene mutation, therefore confirming a diagnosis of hereditary hemochromatosis. He commenced regular venesections in 2019. Despite this treatment, a repeat pituitary MRI in 2024 revealed evidence of iron deposition in the anterior pituitary, which was not reported on the initial scan.

Discussion: Haemochromatosis is a typically an autosomal recessive disorder in which mutations in the HFE gene lead to abnormal production of hepcidin, the hormone which regulates iron absorption. Excess iron is deposited in body tissues, which can lead to widespread organ dysfunction. Whilst haemochromatosis can cause diabetes and Addison’s disease, the gonadotrophs of the anterior pituitary are disproportionately affected by accumulation of intracellular ferritin due to selective expression of transferrin receptors. Therefore, HH can occur early in the natural history of haemochromatosis, as demonstrated in this Case Study, where the patient had symptoms of androgen deficiency for over 4 years before developing arthritis symptoms due to iron deposition in his joints. Primary testicular dysfunction can also occur due to iron deposition in the testicles. Osteoporosis is prevalent in haemochromatosis due to an increase in the number and size of osteoclasts and the rate of osteoblast apoptosis, so those patients with androgen deficiency are at significantly increased risk.

Question for Consideration: If acquired HH is suspected, should you initially screen for systemic causes for pituitary infiltration (such as haemochromatosis, sarcoidosis)? In this Case Study, infiltration of the pituitary gland was only apparent on the MRI in 2024. This occurred despite receiving regular venesections since 2019, which have so far prevented other systemic complications of haemochromatosis. Why was this the case?