Longitudinal behavior of autoimmune GH deficiency: from childhood to transition age.

BACKGROUND: Some cases of apparently idiopathic GH deficiency (GHD) may be caused by pituitary autoimmunity. OBJECTIVE: To study the variations in pituitary function and antipituitary antibodies (APA) from childhood to transition age in patients with apparently idiopathic GHD. DESIGN: We conducted a longitudinal study. PATIENTS AND METHODS: Pituitary function and APA detection by immunofluorescence were investigated in 24 childhood patients with isolated GHD before starting recombinant GH therapy and after the stopping of this therapy in transition age. Sera of patients positive for APA were processed by double immunofluorescence to identify their pituitary target. RESULTS: At diagnosis, 16 out of 24 patients were APA positive targeting only somatotrophs (group 1), while the remaining eight were APA negative (group 2). When retested off therapy, 12 out of 16 patients in group 1 persisted being APA positive, while the remaining four became negative with recovery of pituitary function. All patients in group 2 persisted being APA negative but still showing GHD. Of the 12 patients persistently APA positive, eight with confirmed GHD showed APA still targeting somatotrophs, whereas four showed APA targeting only gonadotrophs associated with isolated hypogonadotropic hypogonadism (HH). CONCLUSION: Patients with APA at middle but not at high titer in childhood may show a remission of autoimmune GHD in childhood after GH replacement therapy. As APA may shift their target in transition period, an early characterization of APA by double immunofluorescence is advisable in APA positive GHD patients showing delayed puberty, to allow an early diagnosis and an appropriate therapy, thus preventing the progression toward HH.

Late primary autoimmune hypothyroidism in a patient with postdelivery autoimmune hypopituitarism associated with antibodies to growth hormone and prolactin-secreting cells.

BACKGROUND: Pituitary and thyroid autoimmunity can be triggered by pregnancy. We report the first association of combined growth hormone (GH) and prolactin secretion deficiency due to autoimmune damage to GH- and prolactin-secreting cells in a patient with postdelivery lactation failure, presenting subsequently with primary autoimmune hypothyroidism. PATIENT FINDINGS: A 34-year-old woman presented with lactation failure following the delivery of her first child. She had a family history of hypothyroidism without a history of pituitary dysfunction. Physical examination did not show any abnormal findings. Laboratory investigations showed normal gonadotropin levels after the restoration of normal menstrual cycles following pregnancy, normal basal and stimulated cortisol levels, but an impaired GH response to insulin-induced hypoglycemia, and low basal prolactin and insulin-like growth factor-1 concentrations. Thyroid function was normal when initially investigated three months after delivery, but five months later, marked primary hypothyroidism (thyrotropin levels >100 mIU/L) occurred. Immunological investigation revealed the presence of antipituitary antibodies, identified by double immunofluorescence and targeting GH- and prolactin-secreting cells. Antithyroid antibodies, in the normal range three months postpartum, became significantly elevated when the hypothyroidism appeared. Autoimmune hypophysitis is responsible for selective or multiple pituitary-hormone deficiencies, sometimes involving thyrotropin secretion and causing secondary hypothyroidism, but usually associated with hyperprolactinemia. To our knowledge, this is the first observation of autoimmune hypopituitarism involving deficient growth hormone and prolactin secretion in a patient with lactation failure after delivery, subsequently followed by severe primary autoimmune hypothyroidism, thus falling into an unusual constellation of autoimmune polyendocrine syndrome type 3. CONCLUSIONS: Considering the well-known relationship between pregnancy and autoimmunity, an early postdelivery immunological and functional investigation in women presenting with disorders of lactation may be useful to detect potential pituitary and thyroid dysfunction even at a subclinical stage.