Abstract
Familial hypopituitarism represents a clinically and genetically heterogeneous disorder. In a subset of these families, defects in Pit-I, a transcription factor essential for proper pituitary development have been identified as underlying molecular cause. These patients present extreme short stature, GH, PRL and TSH deficiency but intact ACTH, LH and FSH secretion. The pituitary is usually hypoplastic. In this report we describe a consanguineous family (the parents are first cousins) with thirteen siblings. Of the ten living siblings, four (two males and two females) have panhypopituitarism with severe growth failure. They had evidence of growth hormone, prolactin and gonadotropin deficiencies and developed central hypothyroidism late in life. ACTH secretion was normal. Bone age was retarded and dual-photon bone densitometry indicated severe osteoporosis. Combined provocative tests for pituitary hormones indicated blunted responses for GH, LH, FSH and a modest rise in serum PRL and TSH. A clonidine-test failed to induce pituitary GH response. A corticotropin-releasing factor (CRF) provocative test was conducted after 6 months without the use of prednisone with a normal ACTH response after CRF in the affected sibling. Plasma IGF-I and IGF-BP3 were below normal levels. Serum E2 (females) and serum testosterone (males) levels were very low. MRI evaluation of the pituitary indicated pituitary aplasia in all subjects. The phenotype described in this kindred is different from families reported with Pit-1 mutations. However, it resembles previously published kindreds with similar clinical and biochemical findings. The relative preservation of ACTH suggests a genetic defect early in pituitary gland development.
Similar content being viewed by others
References
Rimoin D.L., Merimee T.J., Rabinowitz D., McKusick V.A. Genetic aspects of clinical endocrinology. Rec. Prog. Horm. Res. 24: 365, 1968.
McArthur R.G., Morgan K., Phillips III J.A., Bala M., Klassen J. The natural history of familial hypopituitarism. Am. J. Med. Gen. 22: 553, 1985.
Hooft C., Casneuf J. Familial hypopituitary dwarfism. Helv. Paediatr. Acta 21: 653, 1996.
Ferrier P.E., Stone Jr. E.F. Familial pituitary dwarfism associated with an abnormal sella turcica. Pediatrics 43: 858, 1969.
Sadeghi-Nejad A., Senior B. A familial syndrome of isolated “aplasia” of the anterior pituitary. Diagnostic studies and treatment in the neonatal period. J. Pediatr. 84: 79, 1974.
Medeiros-Neto G.A., Toledo S.P.A., Pupo A.A., Sucupira M. S., Fraige-Filho F., Mattar E., Kastin A.J., Schally A.V. Characterization of the LH response to Luteinizing Hormone-Releasing Hormone (LHRH) in isolated and multiple tropic hormone deficiencies. J. Clin. Endocrinol. Metab. 37: 972, 1973.
Parks J.S., Tenore A., Bongiovanni A.M., Kirkland R.T. Familial hypopituitarism with large sella turcica. N. Engl. J. Med. 298: 698, 1978.
Adler-Bier M., Pertzelan Z., Laron E., Liberman B., Moses S. Multiple pituitary hormone deficiencies in eight siblings of one Jewish Moroccan Family. Acta Paediatr. 68: 401, 1979
McKusick V.A., Rimoin D.L. General Tom Thumb and other midgets. Sci. Am. 217: 102, 1967.
Ferrari C., Toledo S.P.A., Hayashida C., Ezabella M., Abelin N. Familial panhypopituitarism with dwarfism: ACTH and Cortisol responses to DDAVP associated to pituitary hypoplasia. 10th Intern Congr Endocrinol, June 12–15, 1996, San Francisco, USA, Abstract P1-435, p. 243.
Sanchez J.C., Schian A., Perera E., Bawnbach L., Falcone S., Brown M., Parks J., Cleveland W. Analysis of the Pit-1 gene locus in a Jamaican family with combined pituitary hormone deficiency. 10th Intern Congr Endocrinol. June 12–15, 1996, San Francisco, USA, Abstract P2490, p. 527.
Japon M.A., Rubinstein M., Low M.J. In situ hybridization analysis of anterior pituitary hormone gene expression during fetal mouse development. J. Histochem. Cytochem. 42: 1117, 1994.
Li S., Grenshaw E.B., Rawson E.J. Dwarf locus mutants lacking three pituitary cell types results from mutations in the POU-domain gene Pit-1. Nature 347: 765, 1990.
Cohen L.E., Wondisford F.E., Salvatoni A., Maghmie M., Brucker-Davis F., Weintraub B., Radovick S. A “hot spot” in the Pit-1 gene responsible for combined pituitary hormone deficiency: clinical and molecular correlates. J. Clin. Endocrinol. Metab. 80: 679, 1995.
De Zegher F., Pernasetti F., Vanhole C., Devlieger H., van den Berghe G., Martial J.A. The prenatal role of thyroid hormone evidenced by fetomaternal Pit-1 deficiency. J. Clin. Endocrinol. Metab. 80: 3127, 1995.
Woods K.A., Weber A., Clark A.J.L. The molecular pathology of pituitary hormone deficiency and resistance. Bailliere’s Clin. Endocrinol. Metab. 9: 453, 1995.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nogueira, C.R., Leite, C.C., Chedid, E.P.T. et al. Autosomal recessive deficiency of combined pituitary hormones (except ACTH) in a consanguineous Brazilian kindred. J Endocrinol Invest 20, 629–633 (1997). https://doi.org/10.1007/BF03346922
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03346922