Endocrine Abstracts

JOINT2150

Introduction: Phenylketonuria (PKU) is an autosomal recessive disorder that impairs phenylalanine (Phe) metabolism to tyrosine. We present a case of macroprolactinoma in a patient with PKU and explore potential mechanisms linking the conditions.

Case: A 36-year-old man with neonatal-diagnosed classical PKU (compound heterozygous PAH variants) presented to the endocrine clinic with fatigue, low mood, and erectile dysfunction. He had low lumbar spine BMD (Z-score -2. 5), managed with bisphosphonates. Phe concentrations were often above the 600 umol/l target, typically ranging from 550–800 umol/l. Examination showed BMI 32 kg/m², bilateral gynaecomastia, and sparse body hair. Labs confirmed secondary hypogonadism: total testosterone 6. 3 nmol/l, free testosterone 0. 15 nmol/l, LH 1. 23 IU/l, FSH 2. 3 IU/l. Prolactin was elevated at 11, 649 mIU/l (RR 73–407), with macroprolactin excluded. Remainder of pituitary function and calcium concentrations were normal. Family history was negative for pituitary disease. MRI revealed a 17 mm right-sided pituitary macroadenoma. Following initiation of Cabergoline 0. 25 mg weekly, prolactin declined to 1, 421 IU/l at four weeks and 590 IU/l at three months. Total testosterone rose to 10. 3 nmol/l after six months, with symptomatic improvement.

Discussion: Patients with PKU may have impaired neurotransmitter production due to low plasma and brain tyrosine. Elevated Phe levels further deplete brain tyrosine by competing for blood-brain barrier transport, reducing dopamine synthesis. PET studies confirm reduced dopamine production in PKU, even with mildly elevated Phe. Since dopamine inhibits prolactin secretion, low levels result in increased prolactin. Therefore, suboptimal metabolic control in PKU is typically associated with modest prolactin elevations (~1, 500 mIU/l). However, the marked hyperprolactinemia in this case suggests the alternative pathology of prolactinoma. Dopamine is thought to inhibit lactotroph proliferation, and animal models link chronic dopamine deficiency, possibly via reduced D2 receptor stimulation, to pituitary tumorigenesis. However, human data are lacking, necessitating further research on whether PKU-related dopamine deficiency could increase pituitary tumour risk. Bone health is an important concern in PKU. While PKU patients generally have lower BMD Z-scores than controls, most remain within the normal range. However, around 10% have a Z-score below -2, suggesting low BMD. These cases warrant further evaluation for secondary causes.

Conclusion: While mild hyperprolactinemia is common in PKU, markedly elevated prolactin levels should prompt further investigation. This case also highlights the importance of investigating low BMD in PKU, as its underlying causes may be multifactorial. Further research is needed to explore the link between PKU-related dopamine deficiency and pituitary tumorigenesis.