Isolated prolactin deficiency associated with serum autoantibodies against prolactin-secreting cells

Abstract

Context: Isolated prolactin (PRL) deficiency is a rare entity of unknown etiology manifesting as failure of puerperal lactogenesis.

Objective: The aim of the study was to determine the cause of isolated PRL deficiency in an affected woman.

Design and setting: We examined genetic and autoimmune causes of isolated PRL deficiency at academic medical centers.

Patient: The patient was a 39-year-old woman with puerperal alactogenesis after two deliveries and undetectable PRL. The other pituitary axes, serum calcium levels, and cranial magnetic resonance imaging were normal.

Intervention: Recombinant human PRL (r-hPRL) was administered to the patient.

Main outcome measures: We measured the sequencing of candidate genes and immunofluorescence analysis of autoantibodies directed against pituitary endocrine cells.

Results: There were no rare sequence variants in the genes encoding for PRL, putative PRL-releasing peptide, putative PRL-releasing peptide receptor, or in other genes important for lactotroph lineage development (POU1F1, PROP1, LHX3, LHX4, HESX1, OTX2, and LSD1). The patient serum, on the contrary, contained autoantibodies that specifically recognized a subset of PRL-secreting cells but not PRL itself or any other pituitary cells or hormones. The mother was able to lactate fully after 17 days of treatment with r-hPRL 60 μg/kg every 12 hours, but alactogenesis resumed after treatment was completed.

Conclusions: These studies report a new autoimmune etiology for women with isolated PRL deficiency and puerperal alactogenesis.

Trial registration: ClinicalTrials.gov NCT00181623.

Figure 1.

Serum PRL levels in a woman with isolated PRL deficiency. Serum PRL was measured during breast pumping (indicated by the time from −3 to 0 h) and up to 8 hours after administration of r-hPRL (60 μg/kg every 12 h). Measurements were performed on injection days 1 (closed circles), 7 (closed triangles), and 28 (closed diamonds), as well as 1 week after the last r-hPRL injection (d 35, open squares).

Figure 2.

The patient autoantibodies recognize a specific subset of PRL-secreting cells in double immunofluorescence experiments using human pituitary as the substrate. Each horizontal series of 3 panels represents the staining obtained using only the patient serum (left panels), only a commercial anti-hormone antibody (center panels), or the two combined (right panels). The top 3 panels represent the experiment with the anti-PRL antibody. It shows that the patient antibodies recognize some PRL-secreting cells that are also recognized by the commercial anti-PRL antibody, and thus appear yellows when the two images are merged (top right panel, arrow heads). It also shows that there are other PRL-secreting cells that are not recognized by the patient serum (top right panel, arrows). Performing the same experiments with commercial antibodies to GH (second row), ACTH (third row), TSH (fourth row), or FSH (fifth row) showed no colocalization of the staining.

Figure 3.

Preabsorption of the patient serum and the commercial anti-PRL antibody using r-hPRL. This preabsorption abolished the signal from anti-PRL antibody (lower right panel) but did not affect the recognition by the patient serum (lower left panel), indicating that the autoantigen(s) recognized by the patient was not PRL itself.