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The Pituitary Gland in the Laurence-Moon Syndrome

1987; Elsevier BV; Volume: 62; Issue: 3 Linguagem: Inglês

10.1016/s0025-6196(12)62445-8

1942-5546

Michael Whitaker, Bernd W. Scheithauer, Kálmán Kovács, Raymond V. Randall, Chaim M. Bell, Haruo Okazaki,

Cellular transport and secretion

The apparent hypogonadism in patients with the Laurence-Moon syndrome has been variably attributed to unresponsiveness of target organs to gonadal hormones, primary end-organ failure, hypothalamic dysfunction, or pituitary failure. We report the first immunocytologic study of the pituitary gland in this rare disorder. No morphologic abnormalities were noted. The numbers and immunoreactivities of adenohypophyseal cell types were normal. No microscopic abnormalities were evident in the hypothalamus and target organs. The results of our study are consistent with recent biochemical data that suggest that pituitary function is normal in patients with this syndrome. The apparent hypogonadism in patients with the Laurence-Moon syndrome has been variably attributed to unresponsiveness of target organs to gonadal hormones, primary end-organ failure, hypothalamic dysfunction, or pituitary failure. We report the first immunocytologic study of the pituitary gland in this rare disorder. No morphologic abnormalities were noted. The numbers and immunoreactivities of adenohypophyseal cell types were normal. No microscopic abnormalities were evident in the hypothalamus and target organs. The results of our study are consistent with recent biochemical data that suggest that pituitary function is normal in patients with this syndrome. The Laurence-Moon syndrome was originally described in 1866 as a combination of pigmentary retinopathy, mental retardation, spastic paraplegia, and hypogonadism.1Laurence JZ Moon RC Four cases of “retinitis pigmentosa” occurring in the same family and accompanied by general imperfections of development.Ophthalmic Rev. 1866; 2: 32-41Google Scholar An allied entity subsequently described by Bardet2Bardet G: Sur un syndrome d'obesite congenitale avec polydactylie et retinite pigmentaire (contribution a l'etude des formes cliniques de l'obesite hypophysaire). Paris, Faculte de Medicine de Paris, Thesis No. 470, 1920Google Scholar and by Biedl3Biedl A Ein Geschwisterpaar mit adiposo-genitaler Dystrophie.Dtsch Med Wochenschr. 1922; 48: 1630Google Scholar is characterized by the addition of obesity and digital anomalies, including Polydactyly, to the original features. Thus, the designation Laurence-Moon-Bardet-Biedl syndrome has been applied to patients who exhibit all the aforementioned characteristics. Some confusion has arisen because complete and incomplete types of these disorders have been described; however, one common physical finding in almost all affected patients seems to be the presence of hypogonadism.4Toledo SPA Medeiros-Neto GA Knobel M Mattar E Evaluation of the hypothalamic-pituitary-gonadal function in the Bardet-Biedl syndrome.Metabolism. 1977; 26: 1277-1291Abstract Full Text PDF PubMed Scopus (26) Google Scholar Hypogonadism is the major endocrine abnormality associated with the Laurence-Moon-Bardet-Biedl syndrome. The pathogenesis of the hypogonadism remains unknown; however, target insensitivity to gonadal hormones, primary end-organ failure, and pituitary failure or hypothalamic dysfunction have been postulated as causes of the endocrine stigmas of the syndrome.4Toledo SPA Medeiros-Neto GA Knobel M Mattar E Evaluation of the hypothalamic-pituitary-gonadal function in the Bardet-Biedl syndrome.Metabolism. 1977; 26: 1277-1291Abstract Full Text PDF PubMed Scopus (26) Google Scholar, 5Mozaffarian G Nakhjavani MK Farrahi A The Laurence-Moon-Bardet-Biedl syndrome: unresponsiveness to the action of testosterone, a possible mechanism.Fertil Steril. 1979; 31: 417-422PubMed Google Scholar, 6Bowen P Ferguson-Smith MA Mosier D Lee CSN Butler HG The Laurence-Moon syndrome: association with hypogonadotrophic hypogonadism and sex-chromosome aneuploidy.Arch Intern Med. 1965; 116: 598-604Crossref PubMed Scopus (18) Google Scholar, 7Reinfrank RF Nichols FL Hypogonadotrophic hypogonadism in the Laurence-Moon syndrome.J Clin Endocrinol Metab. 1964; 24: 48-53Crossref PubMed Scopus (20) Google Scholar, 8Oettlé AG Rabinowitz D Seftel HC The Laurence-Moon syndrome with germinal aplasia of the testis: report of a case and review.J Clin Endocrinol Metab. 1960; 20: 683-699Crossref PubMed Scopus (11) Google Scholar, 9Chang RJ Davidson BJ Carlson HE Lu JKH Judd HL Hypogonadotropic hypogonadism associated with retinitis pigmentosa in a female sibship: evidence for gonadotropin deficiency.J Clin Endocrinol Metab. 1981; 53: 1179-1185Crossref PubMed Scopus (12) Google Scholar, 10Pérez-Palacios A Uribe M Scaglia H Lisker R Pasapera A Maillard M Medina M Pituitary and gonadal function in patients with the Laurence-Moon-Biedl syndrome.Acta Endocrinol (Copenh). 1977; 84: 191-199PubMed Google Scholar In much of the early literature, conclusions about the cause of the hypogonadism were based on measurements of urinary gonadotropins, and the results were frequently conflicting.7Reinfrank RF Nichols FL Hypogonadotrophic hypogonadism in the Laurence-Moon syndrome.J Clin Endocrinol Metab. 1964; 24: 48-53Crossref PubMed Scopus (20) Google Scholar, 8Oettlé AG Rabinowitz D Seftel HC The Laurence-Moon syndrome with germinal aplasia of the testis: report of a case and review.J Clin Endocrinol Metab. 1960; 20: 683-699Crossref PubMed Scopus (11) Google Scholar Recent studies have evaluated the hypothalamus-pituitary-gonadal axis more systematically, but these reports are too few, and in some cases contradictory, to offer a satisfactory explanation for the hypogonadism.4Toledo SPA Medeiros-Neto GA Knobel M Mattar E Evaluation of the hypothalamic-pituitary-gonadal function in the Bardet-Biedl syndrome.Metabolism. 1977; 26: 1277-1291Abstract Full Text PDF PubMed Scopus (26) Google Scholar, 5Mozaffarian G Nakhjavani MK Farrahi A The Laurence-Moon-Bardet-Biedl syndrome: unresponsiveness to the action of testosterone, a possible mechanism.Fertil Steril. 1979; 31: 417-422PubMed Google Scholar, 9Chang RJ Davidson BJ Carlson HE Lu JKH Judd HL Hypogonadotropic hypogonadism associated with retinitis pigmentosa in a female sibship: evidence for gonadotropin deficiency.J Clin Endocrinol Metab. 1981; 53: 1179-1185Crossref PubMed Scopus (12) Google Scholar, 10Pérez-Palacios A Uribe M Scaglia H Lisker R Pasapera A Maillard M Medina M Pituitary and gonadal function in patients with the Laurence-Moon-Biedl syndrome.Acta Endocrinol (Copenh). 1977; 84: 191-199PubMed Google Scholar Testicular morphologic features have been assessed in several communications,4Toledo SPA Medeiros-Neto GA Knobel M Mattar E Evaluation of the hypothalamic-pituitary-gonadal function in the Bardet-Biedl syndrome.Metabolism. 1977; 26: 1277-1291Abstract Full Text PDF PubMed Scopus (26) Google Scholar, 5Mozaffarian G Nakhjavani MK Farrahi A The Laurence-Moon-Bardet-Biedl syndrome: unresponsiveness to the action of testosterone, a possible mechanism.Fertil Steril. 1979; 31: 417-422PubMed Google Scholar, 6Bowen P Ferguson-Smith MA Mosier D Lee CSN Butler HG The Laurence-Moon syndrome: association with hypogonadotrophic hypogonadism and sex-chromosome aneuploidy.Arch Intern Med. 1965; 116: 598-604Crossref PubMed Scopus (18) Google Scholar, 7Reinfrank RF Nichols FL Hypogonadotrophic hypogonadism in the Laurence-Moon syndrome.J Clin Endocrinol Metab. 1964; 24: 48-53Crossref PubMed Scopus (20) Google Scholar, 8Oettlé AG Rabinowitz D Seftel HC The Laurence-Moon syndrome with germinal aplasia of the testis: report of a case and review.J Clin Endocrinol Metab. 1960; 20: 683-699Crossref PubMed Scopus (11) Google Scholar, 11Francke C The gonads in the Laurence-Moon-Biedl syndrome: three case reports with one partial autopsy.J Clin Endocrinol. 1950; 10: 108-112Crossref Scopus (11) Google Scholar but very little information is available regarding the morphologic characteristics of the pituitary gland in patients with the Laurence-Moon syndrome.12McLoughlin TG Shanklin DR Pathology of Laurence-Moon-Bardet-Biedl syndrome.J Pathol Bacteriol. 1967; 93: 65-79Crossref PubMed Scopus (33) Google Scholar, 13Anderson NL The Laurence-Moon-Biedl syndrome: case report with complete autopsy.J Clin Endocrinol. 1941; 1: 905-911Crossref Scopus (9) Google Scholar In this report, we describe the morphologic and immunocytochemical features of the pituitary gland of such a patient. The neuro-ophthalmologic aspects of this case have been reported previously.14Kearns TP Sayre GP Retinitis pigmentosa, external ophthalmoplegia, and complete heart block: unusual syndrome with histologic study in one of two cases.Arch Ophthalmol. 1958; 60: 280-289Crossref Scopus (557) Google Scholar At age 17 years, the patient underwent evaluation because of episodic loss of consciousness. At birth, which had necessitated forceps application, the patient weighed 4.1 kg and was 67.6 cm long. He was able to sit at age 6 months and was walking, had a limited vocabulary, and weighed 15.9 kg at 1 year. When the patient was 3 years old, the parents noted that both of his eyelids were ptotic. Divergent strabismus and loss of hearing had been gradually increasing in severity. He was somewhat shorter than other children, a persistent condition. At age 4 years, he had gait difficulties, which were attributed to loss of vision in the lower visual fields and difficulty in seeing to the right. By 5 years of age, the child was physically inactive and had difficulty in running and jumping. At age 17 years, the patient began experiencing episodes of unconsciousness every 2 to 10 days, occurring one to three times per day. These episodes were preceded by hyperventilation and visual disturbances. The unconsciousness lasted for as long as 15 minutes. No motor seizure activity or urinary or fecal incontinence was noted. Frequently, the patient awoke without residual neurologic deficits. The progressive visual loss, progressive deafness, retarded growth rate, and mental retardation (indirectly assessed by poor scholastic abilities) had persisted from age 3 to 17 years. The family history was unremarkable. There was no history suggestive of glucose intolerance. When the patient was 17 years old, neurologic examination revealed bilateral temporal visual field defects, considerably worse in the right eye. Streaks of depigmentation suggestive of retinitis pigmentosa were noted on funduscopy, and hearing loss was severe bilaterally. Bilateral moderate ptosis and dysfunction of cranial nerves IV and VI were evident. Minimal hyporeflexia was noted in the biceps, brachioradial, and triceps muscle groups. Retarded growth was again noted (height less than 152.5 cm). The genitalia were small, and gynecomastia was apparent. The results of a general physical examination were otherwise unremarkable. Electroencephalography revealed a nonspecific, generalized, grade 3 dysrhythmia, consistent with a disturbance arising from a lesion near the midline of the brain. Visual acuity was decreased bilaterally (20/60 for the left eye and 20/40 for the right eye). Electrocardiography demonstrated complete atrioventricular dissociation with a ventricular rate of 37/min. The following laboratory data were recorded: hemoglobin, 15 g/dl; leukocyte count, 5,700/mm3 with a normal differential; and fasting blood glucose, 78 mg/dl. The findings on urinalysis were unremarkable. During hospitalization, the patient experienced three episodes of unexplained unconsciousness and cardiac arrest, the latter resulting in death. The pituitary gland was fixed in 10% formalin and processed routinely for light microscopy. Microsections (5 μm) were stained with hematoxylin-eosin, Gomori's reticulin, and periodic acid-Schiff. Other endocrine organs (including the thyroid, adrenals, and testes), the breasts, eyes, and extraocular muscles were examined only with use of hematoxylin-eosin stain. The brain was cut in the coronal plane, and multiple microsections of the hypothalamus were stained with hematoxylin-eosin and examined. Serial microsections of the pituitary gland were stained immunocytochemically by the avidin-biotin-peroxidase complex technique.15Hsu S-M Raine L Fanger H Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures.J Histochem Cytochem. 1981; 29: 577-580Crossref PubMed Scopus (13453) Google Scholar Antisera were to growth hormone (DAKO), dilution 1:100; prolactin (donated by Dr. H. G. Friesen, University of Manitoba, Winnipeg, Manitoba), dilution 1:4,000; corticotropin (donated by the National Institutes of Health), dilution 1:2,000; follicle-stimulating hormone and luteinizing hormone (donated by the National Institutes of Health), dilution 1:1,000; thyrotropic hormone (donated by Bio-Rad Laboratories, Richmond, California), dilution 1:5,000; and α-subunit (donated by the National Institutes of Health), dilution 1:2,000. The findings at general autopsy included small testes, atrophy of the thymus and thyroid glands, and bilateral gynecomastia. In the brain, atrophy of the substantia nigra and pronounced vascular siderosis were noted. Retinal pigmentary degeneration was confirmed. Severe degenerative changes in the muscles of the eyes, evident bilaterally, seemed to represent a primary muscle disease rather than the result of denervation.14Kearns TP Sayre GP Retinitis pigmentosa, external ophthalmoplegia, and complete heart block: unusual syndrome with histologic study in one of two cases.Arch Ophthalmol. 1958; 60: 280-289Crossref Scopus (557) Google Scholar Light microscopy disclosed no microscopic abnormality of the grossly normal anterior pituitary gland. The relative proportions of acidophilic, basophilic, and chromophobic cells seemed to be normal. By the immunoperoxidase staining technique, all the adenohypophyseal cell types were well represented (Fig. 1). Somatotropic, lactotropic, corticotropic, and luteinizing hormone-containing cells were normal in number and cytologic appearance. Thyrotropic cells and cells containing follicle-stimulating hormone or α-subunit seemed to be somewhat increased in number but had no structural alterations. No adenoma was encountered.Fig. 1Histologic sections from anterior pituitary, demonstrating normal cellular morphologic features (A) and normal cellular densities of lactotropic (B), somatotropic (C), and corticotropic (D) cells. (A, Hematoxylin-eosin; x250. B-D, Avidin-biotin-peroxidase technique; x250.)Show full captionHistologic sections from anterior pituitary, demonstrating normal cellular densities of gonadotropic cells elaborating luteinizing hormone (E) and follicle-stimulating hormone (F), thyrotropic cells (G), and α-subunit-producing glycoprotein cells (H). (E-H, Avidin-biotin-peroxidase technique; x250.)View Large Image Figure ViewerDownload (PPT) Histologic sections from anterior pituitary, demonstrating normal cellular densities of gonadotropic cells elaborating luteinizing hormone (E) and follicle-stimulating hormone (F), thyrotropic cells (G), and α-subunit-producing glycoprotein cells (H). (E-H, Avidin-biotin-peroxidase technique; x250.) Externally, the brain was normal. Coronal sections showed no abnormality of the hypothalamus. Serial microsections of the hypothalamus disclosed both normal distribution and normal cellularity of nuclei; no neuronal degeneration or gliosis was evident. In the globus pallidus, iron deposits were noted within the walls of blood vessels and in the form of minute concretions about capillaries. Occasional vessels were surrounded by macrophages that contained hemosiderin pigment. A portion of the posterolateral substantia nigra had loss of pigmented neurons, perivascular collections of pigment, and reactive astrocytosis. The white matter, particularly in the cerebral hemispheres, had mild diffuse fibrillary gliosis and scattered neurons somewhat in excess of the number usually encountered in patients of this age. The testes, although small, had evidence of only mild interstitial fibrosis and a reduction of interstitial cells. Spermatogenesis was normal (Fig. 2 A). The prostate was normal grossly and microscopically. Microsections of the breasts showed the characteristic features of gynecomastia (Fig. 2 B). The thyroid and adrenal glands were normal grossly and microscopically. Gross sections of both eyes revealed a diffuse mottling posteriorly. Microscopy disclosed a diffuse depletion of pigment granules of the retinal pigment epithelium (Fig. 3 A). This abnormality was most notable in a peripapillary location. There was no evidence of pigment migration into the retina. The photoreceptor elements were diffusely reduced in number. The extraocular muscles had myopathic changes, including a diffuse random distribution of atrophic fibers (Fig. 3 B). The nerve elements appeared normal. This case clearly represents an example of the Laurence-Moon syndrome. Although not obese, the patient had evidence of pigmentary retinopathy and mental retardation. The small size of the testes suggested hypogonadism; however, no biochemical studies were undertaken to support this supposition, and the testes had no major histologic abnormalities. The absence of obesity and digital anomalies suggests that this patient should not be classified in the category of patients described by Bardet2Bardet G: Sur un syndrome d'obesite congenitale avec polydactylie et retinite pigmentaire (contribution a l'etude des formes cliniques de l'obesite hypophysaire). Paris, Faculte de Medicine de Paris, Thesis No. 470, 1920Google Scholar and Biedl.3Biedl A Ein Geschwisterpaar mit adiposo-genitaler Dystrophie.Dtsch Med Wochenschr. 1922; 48: 1630Google Scholar Histopathologic findings of the eyes in patients with the Laurence-Moon syndrome have varied from widespread loss of the retinal pigment epithelium and photoreceptor layer14Kearns TP Sayre GP Retinitis pigmentosa, external ophthalmoplegia, and complete heart block: unusual syndrome with histologic study in one of two cases.Arch Ophthalmol. 1958; 60: 280-289Crossref Scopus (557) Google Scholar to normal posterior retinal pigment epithelium but with peripheral partial loss of the pigment epithelium and photoreceptor layer.16Curtin VT: Case presentation at the Association of Ophthalmic Alumni of the Armed Forces Institute of Pathology, Washington, D.C., June 1973Google Scholar The abnormal change in the extraocular muscles has been shown to be subsarcolemmal accumulation of mitochondria or ragged-red fibers.17Olson W Engel WK Walsh GO Einaugler R Oculocraniosomatic neuromuscular disease with “ragged-red” fibers: histochemical and ultrastructural changes in limb muscles of a group of patients with idiopathic progressive external ophthalmoplegia.Arch Neurol. 1972; 26: 193-211Crossref PubMed Scopus (262) Google Scholar This change, however, is found in a variety of disorders and is thus nonspecific.18Eshaghian J Anderson RL Weingeist TA Hart MN Cancilla PA Orbicularis oculi muscle in chronic progressive external ophthalmoplegia.Arch Ophthalmol. 1980; 98: 1070-1073Crossref PubMed Scopus (20) Google Scholar Hypogonadism is a major endocrine abnormality associated with the Laurence-Moon or Bardet-Biedl syndrome and is a factor common to both syndromes.1Laurence JZ Moon RC Four cases of “retinitis pigmentosa” occurring in the same family and accompanied by general imperfections of development.Ophthalmic Rev. 1866; 2: 32-41Google Scholar, 3Biedl A Ein Geschwisterpaar mit adiposo-genitaler Dystrophie.Dtsch Med Wochenschr. 1922; 48: 1630Google Scholar The incidence of hypogonadism in male patients with the Laurence-Moon syndrome reportedly ranges from 83 to 85.7%.19Bell J The Laurence-Moon syndrome.in: Penrose LS The Treasury of Human Inheritance. Vol 5: On Hereditary Digital Anomalies, Part III. Cambridge University Press, Cambridge1958: 51-96Google Scholar, 20Klein D Ammann F The syndrome of Laurence-Moon-Bardet-Biedl and allied diseases in Switzerland: clinical, genetic and epidemiological studies.J Neurol Sci. 1969; 9: 479-513Abstract Full Text PDF PubMed Scopus (189) Google Scholar Recent evidence suggests that in many of the previously reported cases the hypogonadism actually may have represented delayed puberty. Hence, the incidence of true hypogonadism may be considerably lower than previously estimated.21Dekaban AS Parks JS Ross GT Laurence-Moon syndrome: evaluation of endocrinological function and phenotypic concordance and report of cases.Med Ann District Columbia. 1972; 41: 687-694PubMed Google Scholar Indeed, even in the present case, delayed puberty may account for the small testicular size. Regardless of the true incidence of hypogonadism or delayed puberty in patients with this disorder, its pathogenesis remains unexplained. Before the development of radioimmunoassay techniques for the measurement of serum gonadotropins, several reports suggested either hypogonadotropic hypogonadism or primary testicular failure as the basis for the observed hypogonadism.6Bowen P Ferguson-Smith MA Mosier D Lee CSN Butler HG The Laurence-Moon syndrome: association with hypogonadotrophic hypogonadism and sex-chromosome aneuploidy.Arch Intern Med. 1965; 116: 598-604Crossref PubMed Scopus (18) Google Scholar, 7Reinfrank RF Nichols FL Hypogonadotrophic hypogonadism in the Laurence-Moon syndrome.J Clin Endocrinol Metab. 1964; 24: 48-53Crossref PubMed Scopus (20) Google Scholar, 8Oettlé AG Rabinowitz D Seftel HC The Laurence-Moon syndrome with germinal aplasia of the testis: report of a case and review.J Clin Endocrinol Metab. 1960; 20: 683-699Crossref PubMed Scopus (11) Google Scholar, 11Francke C The gonads in the Laurence-Moon-Biedl syndrome: three case reports with one partial autopsy.J Clin Endocrinol. 1950; 10: 108-112Crossref Scopus (11) Google Scholar Early data from testicular biopsies are confusing, the histologic changes being compatible with either hypogonadotropic hypogonadism or germinal aplasia.5Mozaffarian G Nakhjavani MK Farrahi A The Laurence-Moon-Bardet-Biedl syndrome: unresponsiveness to the action of testosterone, a possible mechanism.Fertil Steril. 1979; 31: 417-422PubMed Google Scholar, 7Reinfrank RF Nichols FL Hypogonadotrophic hypogonadism in the Laurence-Moon syndrome.J Clin Endocrinol Metab. 1964; 24: 48-53Crossref PubMed Scopus (20) Google Scholar, 8Oettlé AG Rabinowitz D Seftel HC The Laurence-Moon syndrome with germinal aplasia of the testis: report of a case and review.J Clin Endocrinol Metab. 1960; 20: 683-699Crossref PubMed Scopus (11) Google Scholar, 13Anderson NL The Laurence-Moon-Biedl syndrome: case report with complete autopsy.J Clin Endocrinol. 1941; 1: 905-911Crossref Scopus (9) Google Scholar More recent evaluations of the hypothalamus-pituitary-gonadal axis of patients with these disorders suggest that the major defect is related to gonadal failure, end-organ insensitivity to gonadal steroids, or pituitary gonadotropin deficiency. Toledo and associates4Toledo SPA Medeiros-Neto GA Knobel M Mattar E Evaluation of the hypothalamic-pituitary-gonadal function in the Bardet-Biedl syndrome.Metabolism. 1977; 26: 1277-1291Abstract Full Text PDF PubMed Scopus (26) Google Scholar published clear documentation of normal hypothalamus-pituitary endocrine function and testicular morphologic features; these findings suggest that an evolving primary gonadal disorder is present in patients with the Bardet-Biedl syndrome. Mozaffarian and colleagues5Mozaffarian G Nakhjavani MK Farrahi A The Laurence-Moon-Bardet-Biedl syndrome: unresponsiveness to the action of testosterone, a possible mechanism.Fertil Steril. 1979; 31: 417-422PubMed Google Scholar reported similar findings in a patient with the complete Laurence-Moon-Bardet-Biedl syndrome. In their patient, the hypogonadism did not regress, even after several months of testosterone therapy; thus, end-organ resistance to testosterone may be a factor in the pathogenesis of the clinical findings. In a series of three male patients with the Laurence-Moon-Biedl syndrome, Pérez-Palacios and associates10Pérez-Palacios A Uribe M Scaglia H Lisker R Pasapera A Maillard M Medina M Pituitary and gonadal function in patients with the Laurence-Moon-Biedl syndrome.Acta Endocrinol (Copenh). 1977; 84: 191-199PubMed Google Scholar also found a normal pituitary gonadotropin response to stimulation by luteinizing hormone releasing factor, an indication that the lesion was not in the pituitary gland. Conversely, Chang and co-workers9Chang RJ Davidson BJ Carlson HE Lu JKH Judd HL Hypogonadotropic hypogonadism associated with retinitis pigmentosa in a female sibship: evidence for gonadotropin deficiency.J Clin Endocrinol Metab. 1981; 53: 1179-1185Crossref PubMed Scopus (12) Google Scholar demonstrated an impaired gonadotropin response to stimulation by luteinizing hormone releasing factor in three female patients with hypogonadotropic hypogonadism and retinitis pigmentosa, a finding that suggested the presence of a pituitary gonadotropin deficiency. Therefore, in this group of disorders, patients seem to have a variety of potential causes for the hypogonadism. In part, this heterogeneity may reflect discrepancies in categorization of patients. Published data regarding the pathologic changes in the pituitary gland in patients with the Laurence-Moon or Laurence-Moon-Bardet-Biedl syndrome are scarce. An increased number of basophils has been noted in some patients;12McLoughlin TG Shanklin DR Pathology of Laurence-Moon-Bardet-Biedl syndrome.J Pathol Bacteriol. 1967; 93: 65-79Crossref PubMed Scopus (33) Google Scholar, 13Anderson NL The Laurence-Moon-Biedl syndrome: case report with complete autopsy.J Clin Endocrinol. 1941; 1: 905-911Crossref Scopus (9) Google Scholar, 22Griffiths GM The Laurence-Moon-Biedl syndrome: a pathological report.J Neurol Psychiatry. 1938; 1: 1-4Crossref PubMed Google Scholar however, in most instances, no abnormality was apparent by light microscopy.12McLoughlin TG Shanklin DR Pathology of Laurence-Moon-Bardet-Biedl syndrome.J Pathol Bacteriol. 1967; 93: 65-79Crossref PubMed Scopus (33) Google Scholar, 23Brattgård SO The pathology of Laurence-Moon-Biedl syndrome.Acta Pathol Microbiol Scand. 1949; 26: 525-537Crossref PubMed Scopus (12) Google Scholar, 24Ross CF Crome L Mackenzie DY The Laurence-Moon-Biedl syndrome.J Pathol Bacteriol. 1956; 72: 161-172Crossref PubMed Scopus (11) Google Scholar Because routine histologic stains and complex histochemical methods correlate only crudely with hormonal production and provide no useful information about the functional characteristics of the cells of the anterior pituitary,25Scheithauer BW Surgical pathology of the pituitary: the adenomas. Part I.Pathol Annu. 1984; 1: 317-374Google Scholar, 26Scheithauer BW Surgical pathology of the pituitary: the adenomas. Part II.Pathol Annu. 1984; 1: 269-329Google Scholar we undertook immunocytologic studies. The finding of normal morphologic features and hormonal reactivity in our patient supports the recent reports of normal pituitary biochemical function in patients with this disorder.4Toledo SPA Medeiros-Neto GA Knobel M Mattar E Evaluation of the hypothalamic-pituitary-gonadal function in the Bardet-Biedl syndrome.Metabolism. 1977; 26: 1277-1291Abstract Full Text PDF PubMed Scopus (26) Google Scholar, 5Mozaffarian G Nakhjavani MK Farrahi A The Laurence-Moon-Bardet-Biedl syndrome: unresponsiveness to the action of testosterone, a possible mechanism.Fertil Steril. 1979; 31: 417-422PubMed Google Scholar, 10Pérez-Palacios A Uribe M Scaglia H Lisker R Pasapera A Maillard M Medina M Pituitary and gonadal function in patients with the Laurence-Moon-Biedl syndrome.Acta Endocrinol (Copenh). 1977; 84: 191-199PubMed Google Scholar Our results, in conjunction with the physical findings in this case, are consistent with the view that a primary end-organ defect, target organ unresponsiveness to gonadal steroids, or delay in puberty may underlie the hypogonadism. If primary testicular failure is the major endocrinologic lesion in these patients, an increase in cells that secrete follicle-stimulating hormone or luteinizing hormone in the pituitary gland could be anticipated. Although formation of basophilic pituitary adenomas has been substantiated in rats rendered hypogonadal27Griesbach WE Purves HD Basophil cell adenomas in the rat pituitary.Proc Otago Univ Med Sch. 1956; 34: 1-2Google Scholar and an increase in number of basophils has been noted in some cases of the Laurence-Moon-Biedl syndrome, no clear confirmation of gonadotropic hyperplasia, as determined by immunocytochemical staining techniques, has been found in humans with primary hypogonadism (Scheithauer BW, Kovacs KT, Randall RV: Unpublished data). Therefore, in our patient, the pituitary findings may be completely compatible with primary end-organ failure or may indeed represent a delay in puberty, because of his young age at death. Unfortunately, endocrine stimulation tests relevant to this issue were not available at the time of our patient's death (1955). We acknowledge the technical contribution of Rose A. Comero and Nancy Ryan and the secretarial assistance of Jill A. Johnson.