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Constitutionally tall stature with morphological abnormality of the pituitary gland.

We describe two male pubertal cases of constitutionally tall stature (CTS) with an enlarged pituitary gland or pituitary microadenoma. Both patients' basal serum growth hormone (GH) levels were normal. Neither had oversecretion of any other pituitary hormones. However, their serum GH levels were paradoxically increased in response to an intravenous administration of thyrotropin-releasing hormone (TRH). A later GH response to an intravenous administration of luteinizing hormone-releasing hormone (LHRH) was also found in one patient. In addition, oral glucose loading (OGL) caused a late increase in serum GH at 180 min in both patients. Our present findings suggest that endocrinological and morphological abnormalities of the pituitary gland are found in some subjects with CTS during puberty. It is speculated that these paradoxical GH responses are associated with dysregulation of GH secretion. Finally, it is important to investigate whether tall children with morphological abnormalities of the pituitary gland such as our patients are preacromegalic, in which case, given that overproduction of GH secretion may occur in the future, further observation is necessary.

Adenoma↗

Morphology of the pituitary gland in ferrets (Mustela putorius furo) with hyperadrenocorticism.

Pituitary tumours are the cause of hyperadrenocorticism in a variety of species, but the role of the pituitary gland in hyperadrenocorticism in ferrets is not known. In this species, the disease is mediated by the action of excess gonadotrophins on the adrenal cortex and is characterized by an excessive secretion of sex steroids. In this study, the pituitary gland of four healthy control ferrets, intact or neutered, and 10 neutered ferrets with hyperadrenocorticism was examined histologically following immunohistochemical labelling for adrenocorticotrophic hormone, alpha-melanocyte-stimulating hormone, growth hormone, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, and prolactin. Immunohistochemistry revealed that somatotrophs, thyrotrophs and lactotrophs were the most abundant cell types of the pars distalis of the pituitary gland in the healthy ferrets. The distribution of corticotrophs was similar to that in the dog and man. In ferrets, as in dogs, the melanotrophic cell was almost the only cell type of the pars intermedia. Gonadotrophs were found in the pars distalis of neutered, but not intact ferrets. All the ferrets with hyperadrenocorticism had unilateral or bilateral alterations of the adrenal gland. In addition, in the pituitary gland of two of these ferrets a tumour was detected. These tumours were not immunolabelled by antibodies against any of the pituitary hormones, and had characteristics of the clinically non-functional gonadotroph tumours seen in man. In some of the other ferrets low pituitary immunoreactivity for gonadotrophic hormones was detected, which may have been due to the feedback of autonomous steroid secretion by the neoplastic transformation of the adrenal cortex. It is concluded that initially high concentrations of gonadotrophins resulting from castration may initiate hyperactivity of the adrenal cortex. The low incidence of pituitary tumours and the low density of gonadotrophin-positive cells in non-affected pituitary tissue in this study suggest that persistent hyperadrenocorticism is not dependent on persistent gonadotrophic stimulation.

Adenoma↗

Mensuration of the normal pituitary gland from magnetic resonance images in 96 dogs.

The pituitary gland was measured from transverse magnetic resonance T1-weighted images after Gadolinium administration in 96 dogs weighing from 13 to 45 kg. The measurements were done by hand with calipers. The mean (+/- standard deviation) pituitary gland height was 5.1 mm (+/-0.9 mm). The mean width was 6.4 mm (+/- 1.1 mm). The correlation coefficient between pituitary and brain measurements, between pituitary measurement and body weight, and brain measurements and body weight was 0.0 to 0.3. A hyperintense region was present on T1-weighted images in the center of the pituitary gland in 64% of the dogs. At necropsy the pituitary glands were grossly and histologically normal. No pituitary gland measurements were performed at necropsy.

Animals↗

The pituitary gland: embryology, physiology, and pathophysiology.

The pituitary gland, the "master gland" of the body, is composed of endocrine cells, which secrete hormones essential for homeostasis. The gland consists of the adenohypophysis (anterior pituitary) and the neurohypophysis (posterior pituitary), two unique structures that differ anatomically and functionally. The neurohypophysis is innervated by nerve cells in the hypothalamus and forms the connection between it and the pituitary gland. The hypothalamus stimulates release and inhibition of pituitary hormones. The neurohypophysis secretes oxytocin and antidiuretic hormone. The adenohypophysis is composed of three structures: the pars distalis, the pars intermedia, and the pars tuberalis. The anterior pituitary (pars distalis) is responsible for the release of hormones that include growth hormone, prolactin, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, adrenocorticotropic hormone, and melanocyte-stimulating hormone. Disorders of the pituitary are predominately those of insufficient hormone release and may have profound effects on the neonate. The potential causes of and clinical symptomatology that may accompany pituitary hormone insufficiency in the neonatal period are explored.

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A rare expression of neural crest disorders: an intrasphenoidal development of the anterior pituitary gland.

Congenital abnormalities of the pituitary gland are rare and may be associated with midline cranial, orbital, and facial anomalies and with hormonal insufficiency. Here we report a case of asymptomatic, abnormal migration of the adenohypophysis. The normally developed adenohypophysis was located in the sphenoid bone and developed on the intersphenoidal septum, extending from the superior pharyngeal wall to the floor of the sella turcica (craniopharyngeal canal). The abnormal migration of the pituitary gland was isolated without hormonal deficit, brain, or facial developmental anomalies.

Adult↗

Synthesis and secretion of phosphorylated growth hormone by rat pituitary glands in vitro.

Rat anterior pituitary glands were incubated in buffered medium, pH 7.4, containing 32Pi. After incubation the tissue and medium were separated and a post-mitochondrial supernate (PMS) of the tissue homogenate was prepared. Gel filtration of the PMS and medium resulted in a radioactive peak which coincided with the elution volume of authentic rat growth hormone (rGH). Polyacrylamide gel electrophoresis of the radioactive peak under denaturing condition resulted in a protein-staining band having the same mobility as authentic rGH. Autoradiography of the gels revealed radioactivity precisely at the position of growth hormone as well as elsewhere. The specific radioactivity of the PMS [32P]GH was estimated to be 5 to 10 times greater than that of tissue [32P]GH. These results indicate that phosphorylated GH is synthesized and secreted by pituitary glands in vitro.

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Neurotransmitter effects on release of prolactin and growth hormone in vitro from pituitary glands of the pigeon, Columba livia.

Single pigeon anterior pituitary glands were incubated with or without a hypothalamus in media containing various drugs. Release of prolactin and growth hormone was quantified by an electrophoretic-densitometric method. The hypothalamus stimulated release of both prolactin and growth hormone from the pituitary gland. Dopamine did not affect hormone release from pituitary glands incubated alone, but inhibited hypothalamus-stimulated release of prolactin and augmented hypothalamus-stimulated release of growth hormone in a dose-related manner. The effects of dopamine were reversed by its antagonist, pimozide. Serotonin stimulated release of prolactin and inhibited release of growth hormone from pituitary-hypothalamus co-incubations, and these effects were blocked by its antagonist, methysergide. Thyrotrophin releasing hormone (TRH) stimulated release of both hormones directly from pituitary glands incubated alone. Dopamine now inhibited TRH-stimulated release of prolactin, without affecting TRH-stimulated release of growth hormone. These results indicate that the neurotransmitters, dopamine and serotonin, affect the in-vitro release of factors from the hypothalamus which control the secretion of prolactin and growth hormone. In addition, dopamine may inhibit release of prolactin directly from the pituitary gland, but only when secretion of prolactin is high initially.

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Pituitary gland function after disconnection from direct hypothalamic influences in the sheep.

A surgical procedure is described for isolating the pituitary gland from hypothalamic influences in sheep. The procedure results in total deafferentation of the stalk and median eminence but maintains the blood supply to the pituitary gland. The median eminence, pituitary stalk and anterior face of the pituitary gland were exposed by a transnasal, transphenoidal approach. In early studies section of the pituitary stalk as close as possible to the pituitary gland caused almost total infarction of the gland. Attempts were made to disconnect the pituitary gland from the hypothalamus by section immediately above the lateral inputs of the superior hypophyseal arteries but variable results were obtained, always with infarction of part of the pars distalis. When the pituitary gland was disconnected from the hypothalamus by entering the median eminence above the portal circulation and evacuating the nervous tissue of the tuber cinereum, (hypothalamo-pituitary disconnection; HPD), a small area of infarction was found in the pars distalis of only 1/10 cases. HPD effectively disconnected the pituitary gland from hypothalamic control whilst the pars distalis was not deprived of its blood supply. Complete severance of hypothalamo-pituitary connections also caused atrophy of the pars nervosa and enlargement of the cells of the pars intermedia. Following HPD, plasma LH and FSH concentrations diminished and plasma prolactin concentrations rose. On the day after surgery there were no LH, FSH or prolactin responses to 50 micrograms (i.m.) of oestradiol benzoate indicating the functional isolation of the pituitary gland from the hypothalamus. The isolated pituitaries were capable of responding to gonadotropin releasing hormone by LH release. Disconnection of the pituitary gland from the hypothalamus by subpial deafferentation provides a good in vivo isolated pituitary model in the sheep.

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Normal and abnormal pituitary glands: gadopentetate dimeglumine-enhanced MR imaging.

Dynamic magnetic resonance (MR) imaging with a 1.5-T superconductive unit was used in the evaluation of nine normal pituitary glands and 10 pituitary adenomas, including four microadenomas and six macroadenomas. Seven to 10 images were obtained every 20-30 seconds with use of the spin-echo technique after rapid injection of gadopentetate dimeglumine. The earliest contrast material enhancement of normal structures was seen in the infundibulum and posterior lobe of the pituitary gland at 20 seconds, followed by gradual contrast material enhancement of the anterior lobe of the pituitary gland from the junction of the infundibulum to the peripheral portion of the anterior lobe of the pituitary gland within 80 seconds after gadopentetate dimeglumine injection. The peak enhancement of pituitary adenomas occurred at 60-200 seconds, usually after the most marked enhancement of the normal pituitary gland. Microadenomas are best visualized at earlier phases of gadopentetate dimeglumine-enhanced dynamic imaging, with signal intensity lower than that seen on images of normal pituitary glands.

Adenoma↗

Normal pituitary gland: 2. Microscopic anatomy-CT correlation.

Pituitary microadenomas may present with subtle or no mass effect. They may appear lucent, dense, or heterogeneous on computed tomographic (CT) images. The normal pituitary gland may also have a nonhomogeneous CT appearance with intermingled lucent and dense areas. This heterogeneity is related in part to microscopic variation within the anterior and posterior lobes. Thirteen autopsy specimens of the pituitary gland were examined by coronal CT and histologically sectioned in similar coronal planes. The CT-lucent and CT-dense areas of the anterior and posterior lobes were correlated with corresponding areas on microscopic examination. To determine the effects of contrast infusion during CT, density measurements of lucent and dense areas in the anterior lobes of 26 normal contrast-enhanced pituitary glands in vivo were compared with density measurements of adjacent vascular structures at the time of scanning. Microscopic features corresponding to increased CT density in the anterior lobe included increased tissue compactness and increased cellular granularity, both of which usually occurred together in areas composed of tightly compacted and heavily granulated acidophilic cells. Conversely, microscopic features corresponding to decreased CT density in the anterior lobe included decreased tissue compactness and decreased cellular granularity, both of which frequently occurred together in areas containing chromophobic and/or mildly to moderately granulated basophilic cells. The degree of contrast enhancement within the anterior lobe appeared primarily to depend on vascularity, which in turn often depended on the degree of tissue compactness. In the posterior lobe, CT-lucent areas appeared to correspond to less compact and/or less vascular neurohypophyseal tissue.

Adenoma↗

Sexually differentiated role of calcium ions in chicken GnRH-I-stimulated release of LH from anterior pituitary glands from adult domestic chickens.

Continuous perifusion of quartered anterior pituitary glands from juvenile and adult chickens of both sexes with chicken gonadotrophin-releasing hormone-I (cGnRH-I) stimulated a spike-plateau profile of luteinizing hormone (LH) secretion. When perifused in Ca(2+)-free medium, pituitary glands from juveniles of both sexes and from adult cockerels but not those from laying hens, released LH in response to cGnRH-I. This release occurred at the same time as the spike phase of the response seen in the presence of extracellular Ca2+ and was not accompanied by a plateau phase of secretion. The magnitude of the plateau but not the spike phase of LH secretion from pituitary glands from adult males and females was reduced by the L-type Ca2+ channel blocker, nifedipine. This suggests that the mechanism of cGnRH-I-induced LH release from pituitary glands from laying hens is independent of mobilization of intracellular Ca2+, and that entry of Ca2+ during the spike phase of LH secretion occurs through non-L-type Ca2+ channels. Both non-L-type and L-type Ca2+ channels operate during the plateau phase of secretion in adults of both sexes. The duration of the spike phase of LH release from pituitary glands from adult cockerels was curtailed in the presence of nifedipine. The spike phase of LH release from the adult cockerel pituitary therefore involves three modes of Ca2+ flux, comprising an intracellular Ca(2+)-dependent component and extracellular components involving Ca2+ entry through L-type and non-L-type Ca2+ channels. The finding that the extracellular Ca(2+)-independent component of cGnRH-I-stimulated LH release from pituitary glands from juvenile hens is not present in adult hens suggests that this difference is related to sexual maturation. The maturational and sexual differences in the LH response to cGnRH-I could be mediated through the high concentrations of plasma 17 beta-oestradiol in adult hens which suppress the mobilization of intracellular stores of Ca2+ in the gonadotrophes.

Animals↗

Intraobserver and interobserver agreement, reproducibility, and accuracy of computed tomographic measurements of pituitary gland dimensions in healthy dogs.

OBJECTIVE: To determine the reproducibility and accuracy of computed tomographic (CT) measurements of pituitary gland dimensions in healthy dogs. ANIMALS: 35 healthy sexually intact adult dogs. PROCEDURES: 2 observers independently viewed CT images of the skull in 35 dogs twice. Pituitary gland height, width, length, and volume and pituitary gland height-to-brain area ratio (P:B ratio) were measured or calculated. Intraobserver and interobserver agreement indexes (AIs) were calculated for pituitary gland dimensions. Computed tomography was performed also on 5 phantoms, and both observers measured phantom dimensions twice. True-value AIs were calculated for the phantom study. RESULTS: The mean +/- SD interobserver AI between observer 1 and 2 for pituitary gland height and the P:B ratio was 0.90 +/- 0.07. The intraobserver AI for pituitary gland height and the P:B ratio was 0.97 +/- 0.04 for observer 1 and 0.94 +/- 0.04 for observer 2. The intra and interobserver AIs for the other dimensions were lower than those for pituitary gland height and the P:B ratio. All phantom dimensions on CT images were underestimated significantly, compared with their true values. CONCLUSIONS AND CLINICAL RELEVANCE: The intra- and interobserver AIs for pituitary gland dimension measurements on CT images were high. However, the same observer preferably should perform serial measurements. Window settings influence pituitary gland dimension measurements, and predetermined window settings are recommended to make comparisons among dogs. Pituitary gland dimension measurements made from CT images in our study underestimated the true values.

Animals↗

Immunohistochemical observations on TSH secreting cells in pituitary glands of goat kids with congenital goitre.

Pituitary glands of normal-termed stillborn goat kids with congenital goitre and normal-termed stillborn goat kids without congenital goitre were examined macroscopically, histopathologically and immunohistochemically. Thyroid glands of these animals were also examined grossly and microscopically. The pituitary glands of kids with goitre were larger than those of normal kids, and on histopathological examination there was hyperplasia of the acidophil cells in the ventral part of the glands. However, it was impossible to distinguish thyroid stimulating hormone (TSH)-secreting cells from other acidophil cells in sections stained with haematoxylin and eosin (HE). Red granules were observed in the cytoplasm of these hyperplastic cells in periodic acid-Schiff (PAS)-stained sections. Sections were also immunostained with an antibody against TSH using the streptavidin-biotin peroxidase technique. Immunohistochemistry revealed TSH-secreting cells to have increased in number in the pituitary glands of kids with congenital goitre because of the extensive proliferation when compared with those of normal kids. The present study indicated that the presence of multiple fetuses (twins or triplets) may be a predisposing factor for congenital goitre.

Animals↗

Distribution of GABA binding site subtypes in rat pituitary gland.

GABAA and GABAB binding sites in rat pituitary gland were investigated using equilibrium binding assays in vitro. Specific binding of both [3H]GABA and [3H]muscimol could be detected in both anterior and neurointermediate lobes, with a relative concentration in the anterior lobe. [3H]GABA binding was discriminated into GABAA and GABAB receptor type binding using baclofen. GABAB sites were detectable in the anterior but not in the neurointermediate lobe. Saturation analysis of [3H]muscimol binding to whole pituitary gland membranes demonstrated that the pituitary contains two classes of GABAA sites differing in affinity, as found in the CNS, although the number of sites is considerably lower than in the CNS.

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Estrogen-induced hyperplasia and neoplasia in the rat anterior pituitary gland. An immunohistochemical study.

Diethylstilbestrol (DES) treatment of weanling F344 female rats resulted in enlarged pituitary glands and diffuse pituitary prolactin (PRL) cell hyperplasia in all animals after 9 and 12 weeks of treatment. Serum PRL was significantly greater than in control rats (P less than 0.001). Immunohistochemical studies showed that most of the pituitary gland cells consisted of PRL cells. Ultrastructural studies showed increased numbers of PRL cells with hyperplasia of the rough endoplasmic reticulum and decreased numbers of secretory granules. There was a decrease in the relative number of growth hormone (GH) and other cell types in the anterior pituitary. Pituitary tumors and normal pituitary glands were dissociated with trypsin and maintained in culture for 3 weeks. The numbers of PRL and GH cells decreased with time in both groups, and there was an increase in the number of fibroblasts. Staining of the culture cells with neuron-specific enolase showed that the anterior pituitary cells were positive for this enzyme, while the fibroblastic cells were negative. When dissociated pituitary cells were cultured in the presence of 10(-9) M DES for 7 days, there was a 42% increase in the number of immunoreactive PRL cells. These results indicate that DES-treated rats provide an excellent model for study of the in vivo and in vitro regulation of pituitary hyperplasia and neoplasia.

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