Endocrine Abstracts

Section 1: Case History: A 28 year old female initially presented to Endocrinology in 2020 with hirsutism and irregular menstruation but reassuring biochemistry. In 2022, she was referred to Gastroenterology with weight loss, vomiting and dyspepsia and found to have severe hyperprolactinaemia. Past medical history included anxiety/depression. Current medication was esomeprazole 40mg OD and mebeverine 135mg TDS. Cyclizine 50mg TDS had previously been prescribed, followed by domperidone 10mg TDS started three weeks prior to gastroenterology review. The patient was not using hormonal contraception and was not pregnant or lactating. She smoked marijuana four times weekly. She had no new signs or symptoms of hyperprolactinaemia or hormone excess.

Section 2: Investigations: Initial biochemistry in 2020 was reassuring with normal thyroid function and gonadotrophins, although prolactin was not checked at this time. Blood tests in November 2022 demonstrated normal thyroid function and gonadotrophins, but prolactin was significantly elevated at 3833 mU/L. Macroprolactin was excluded. Blood tests in December 2022, 20 days after discontinuing domperidone, demonstrated normal pituitary function and normalised prolactin of 211 mU/L. MRI pituitary in December 2022 demonstrated a normal gland with no apparent differential enhancing lesion.

Section 3: Results and treatment: Given the normalised prolactin and no clinical evidence of hyperprolactinaemia, the patient was reassured and discharged from the Endocrinology Clinic.

Section 4: Conclusions and points for discussion: Prolactin levels in females are generally <500 mU/L, with drug induced hyperprolactinaemia usually associated with only modest hyperprolactinaemia, although severe hyperprolactinaemia is well-recognised as a side effect of metoclopramide, risperidone and phenothiazines. Prolactin >2000 mU/L may indicate a pituitary adenoma. Domperidone is a peripherally selective D2-receptor antagonist acting at the lactotrophs of the anterior pituitary to reduce intracellular cyclic AMP thereby increasing prolactin production. It is thought to cause only mild hyperprolactinaemia. Previous work by Bouwers et al demonstrated that a single dose of domperidone might increase prolactin to 157-2638 mU/L with sustained but lower levels of hyperprolactinaemia following two weeks of treatment. Esomeprazole has been suggested as a cause of hyperprolactinaemia in several case reports, potentially by inhibition of CYP3A4 elevating oestrogen levels. Marijuana has been similarly implicated although literature is mixed with reports of decreased, increased and unchanged prolactin associated with cannabinoids. The significant degree of transient hyperprolactinaemia in this patient may have been exacerbated by co-administration of domperidone with long-term esomeprazole and/or by cannabinoid use and resolved with discontinuation of domperidone.