Diseases of the Hypothalamus and Pituitary

Chapter 36 Diseases of the Hypothalamus and Pituitary



John F. Randolph, Rhett Nichols, Mark E. Peterson



NORMAL ANATOMY AND PHYSIOLOGY


The pituitary gland (hypophysis) consists of the neurohypophysis surrounded by the adenohypophysis.




Neurohypophysis


The neurohypophysis, also called the pars nervosa and infundibulum (Fig. 36-1), extends ventrally from the hypothalamus.


image

Figure 36-1 Schematic diagram of a mid-sagittal section through the pituitary gland of a normal dog (A) and cat (B).


(Modified from Dellmann HD: Veterinary Histology: An Outline Text-Atlas. Philadelphia: Lea & Febiger, 1971.)



• It is composed of nerve tracts terminating from nuclei within the hypothalamus.

• Antidiuretic hormone (ADH, vasopressin) and oxytocin, produced by the supraoptic and paraventricular hypothalamic nuclei, travel down the axons to be stored in and secreted from the neurohypophysis.


Adenohypophysis


The adenohypophysis is an embryonic outgrowth of the pharynx connected to the hypothalamus by a vascular network that allows humoral control of adenohypophyseal secretions by the hypothalamus.



• In response to the neurotransmitters, specialized neurosecretory cells within the hypothalamus release factors that control production and secretion of hormones from the adenohypophysis (Table 36-1).

• Hormones produced by target endocrine organs in response to specific adenohypophyseal hormones exert negative feedback (or feedback inhibition) on further elaboration of the hypothalamohypophyseal hormones.
• Because growth hormone (GH), prolactin, and melanocyte-stimulating hormone do not have target endocrine organs to participate in negative feedback controls, releasing and inhibiting factors from the hypothalamus control production of these hormones (see Table 36-1).

• The adenohypophysis is subdivided into the pars distalis, pars tuberalis, and pars intermedia (see Fig. 36-1).

• The pars intermedia, unlike the pars distalis, does not have an extensive blood supply contiguous with the hypothalamus. The cells of the pars intermedia appear to release their hormones in response to dopaminergic and serotonergic innervation.

Table 36-1 ADENOHYPOPHYSEAL HORMONES AND THEIR REGULATORY HYPOTHALAMIC HORMONES

































Adenohypophyseal Hormone Hypothalamic Hormone
Thyroid-stimulating hormone (TSH) Thyrotropin-releasing hormone (TRH)
Adrenocorticotropic hormone (ACTH) Corticotropin-releasing hormone (CRH)
Growth hormone (GH, somatotropin) GH-releasing hormone (GHRH, somatocrinin)
GH release-inhibiting hormone (somatostatin)
Follicle-stimulating hormone (FSH) Gonadotropin-releasing hormone (GnRH)
Luteinizing hormone (LH) Gonadotropin-releasing hormone (GnRH)
Prolactin (lactotropic hormone [LTH]) Prolactin-releasing factor
Prolactin inhibitor (dopamine)
Melanocyte-stimulating hormone (MSH) MSH-releasing hormone (MSH-RH)
MSH release-inhibiting hormone (MSH-RIH)


Adenohypophyseal Cells


These are classified by staining properties of their secretory granules.



• Immunohistochemical staining identifies the specific hormone content of the cells.

• Hematoxylin and eosin staining identifies adenohypophyseal cells as follows:
• Acidophils: Somatotrophs and lactotrophs

• Basophils: Gonadotrophs, corticotrophs, and thyrotrophs

• Chromophobes (cells that do not stain selectively): Degranulated, undifferentiated, or actively synthesizing cells (some investigators consider chromophobes to include corticotrophs)


Alternative Nomenclature


Alternatively, the pituitary gland is composed of the anterior lobe and posterior lobe, with the two lobes separated by the hypophyseal cleft (the residual lumen of Rathke’s pouch) (see Fig. 36-1). The terms anterior and posterior, although anatomically correct for the human pituitary, are not accurate when used to describe the lobes of the feline or canine pituitary gland.



• Anterior lobe: Pars tuberalis (glandular pituitary stalk) and pars distalis

• Posterior lobe: Pars nervosa and pars intermedia


DISEASES OF PITUITARY HORMONE EXCESS




Growth Hormone-Secreting Pituitary Neoplasia: Acromegaly


Excess production of GH causes overgrowth of bone, connective tissue, and viscera. If GH oversecretion (hypersomatotropism) occurs after closure of the epiphyses, acromegaly develops. In acromegaly, only the membranous bones (e.g., nose, mandible, and portions of the vertebrae) increase in length, because the long bones cannot grow longitudinally once the epiphyses close.


GH exerts both direct and indirect effects on the body. The indirect actions of GH, mediated by insulin-like growth factor I (IGF-I), are anabolic and include increased protein synthesis and soft tissue and skeletal growth. In contrast, the direct effects of GH are predominantly catabolic (e.g., lipolysis and restricted cellular glucose transport).



Etiology



• In cats: The major cause of acromegaly is a GH-secreting tumor of the pituitary gland.

• In dogs: Endogenous (diestrus) or exogenous progestogens may cause acromegaly by inducing GH production from the hyperplastic ductular epithelium of the mammary glands.


Key Point


Acromegaly in dogs is caused by progestogens. Feline acromegaly develops from a GH-secreting pituitary tumor.



Clinical Signs



Signalment


• Age: Middle to old age

• Breed: No breed predilection

• Sex: Most acromegalic cats are male, whereas acromegalic dogs are female


General Appearance



Key Point


The clinical features of acromegaly develop so insidiously that they are frequently overlooked.



• Large paws

• Soft tissue swelling of the head and neck with prominent skin folds

• Prognathism due to mandibular enlargement

• Widened interdental spaces

• Macroglossia

• Increase in body size and weight; weight loss in some cases

• Pot-bellied appearance

• Long, thick, or coarse haircoat

• Rapid growth of toenails


Respiratory System


• In cats: Dyspnea as a result of pulmonary edema or pleural effusion from GH-induced cardiac failure.

• In dogs: Excessive panting, exercise intolerance, and inspiratory stridor develop because oropharyngeal soft tissue proliferation compresses the upper airway.


Cardiovascular System

In cats, cardiac involvement includes the following:



• Systolic murmur

• Cardiomegaly

• Congestive heart failure (43%) characterized by pulmonary edema, pleural effusion, or ascites


Endocrine System



Key Point


Some dogs and most cats with acromegaly have insulin-resistant diabetes mellitus.


• Diabetes mellitus and its accompanying clinical signs of polyuria, polydipsia, and polyphagia develop because GH restricts cellular glucose transport. Insulin resistance results and large dosages of insulin (>2.2 U/kg/day) are frequently needed to control the hyperglycemia.

• In acromegalic cats, the growth-promoting effects of GH lead to enlargement of endocrine glands (thyroid, parathyroid, adrenal), but the function of these glands remains normal.

• In contrast, dogs in which acromegaly is caused by chronic administration of progestogens have subnormal basal cortisol concentrations. The glucocorticoid-like activity of these progestogens probably suppresses adrenocorticotropic hormone (ACTH) secretion and causes secondary hypoadrenocorticism.


Skeletal System


• Spondylosis deformans.

• Hyperostosis of the skull.

• Mandibular enlargement (prognathism).

• Arthropathy: Excess GH causes proliferation of cartilage and soft tissue, resulting in widening of the joint space. Some cats develop degenerative arthropathy with time. Acromegalic dogs seem less likely to develop joint problems.


Nervous System


• Growth of the pituitary tumor in feline acromegaly may impinge on brain tissue, causing circling, seizures, or behavioral changes.


Urinary System


• GH excess causes renal hypertrophy and increased glomerular filtration rate and renal plasma flow.

• Renal failure develops in about 50% of acromegalic cats. The kidneys of these cats have mesangial thickening of the glomeruli that may result from the glomerulosclerosis associated with unregulated diabetes mellitus and GH-mediated glomerular hyperfiltration.


Reproductive System


• Dogs with progesterone-induced acromegaly may develop pyometra, mucometra, and mammary gland nodules.


Diagnosis



Basis for a Presumptive Diagnosis of Feline Acromegaly


• Clinical and laboratory features characteristic of acromegaly

• CT or MRI documentation of a pituitary mass

• Normal results on thyroid and adrenal testing


Basis for a Presumptive Diagnosis of Canine Acromegaly


• Characteristic clinical and laboratory findings

• Exposure to a progestogen source and improvement in clinical signs following removal of that progestogen source

• No evidence of spontaneous hyperadrenocorticism on adrenal testing


Key Point


Suspect acromegaly in female dogs receiving progestogens and in intact female dogs that develop diabetes mellitus or laryngeal stridor due to soft tissue overgrowth. Suspect acromegaly in cats with insulin-resistant diabetes mellitus.



Physical Examination

Look for the clinical signs listed previously. To confirm enlargement of the head and paws, redundant skin folds, and prognathism, compare the animal’s appearance with earlier photographs of the animal, if possible.



Routine Laboratory Tests


• Severe hyperglycemia and glycosuria are found in most cats and some dogs with acromegaly. Despite the poorly regulated diabetic state of most acromegalic cats and the enhancement of ketogenesis by GH, ketosis rarely develops.

• Less frequently, increases in cholesterol, alanine aminotransferase (ALT), and serum alkaline phosphatase (ALP) may be caused by the diabetic state. However, in many acromegalic dogs without diabetes, ALP activity is increased.

• Mild to moderate hyperproteinemia occurs in 50% of acromegalic cats, but the serum protein electrophoretic pattern is normal.

• Hyperphosphatemia may develop secondary to increased renal tubular reabsorption of phosphorus promoted by GH.

• There may be a stress leukogram, anemia (in dogs, the cause is uncertain), or mild erythrocytosis (in cats, due to GH-stimulated erythropoiesis).

• Acromegalic cats that develop renal failure have persistent proteinuria (100-300 mg/dl) with dilute urine specific gravity (USG) (1.015-1.025).


Radiography

Examine for the following:



• Visceral enlargement (cardiomegaly, hepatomegaly, renomegaly)

• Soft tissue proliferation (oropharyngeal region, head, limbs)

• Bony changes (spondylosis, hyperostosis of the calvarium, periarticular periosteal reaction)

• Left ventricular and septal hypertrophy in acromegalic cats with cardiomegaly (by echocardiogram)


Other Diagnostic Imaging

Magnetic resonance imaging (MRI) and computed tomography (CT) may be helpful in identifying a possible pituitary tumor (see Chapter 4 for an overview of CT and MRI).



Growth Hormone Determination

Increased circulating GH concentrations confirm a diagnosis of acromegaly. However, GH concentrations may be normal in some acromegalic patients and may be increased in a variety of other diseases.



• Increased GH concentration in the presence of profound hyperglycemia supports a diagnosis of acromegaly because hyperglycemia would normally be expected to suppress GH secretion.

• Alternatively, an integrated 24-hour GH concentration determined by frequent sampling throughout the day may be more indicative of GH hypersecretion than solitary determinations.

• Validated GH radioimmunoassays are not widely available for the dog or cat. Utrecht University in the Netherlands measures canine and feline GH concentrations in plasma. However, until such assays are routinely obtainable, diagnose acromegaly presumptively (see “Diagnosis” on page 400).


Insulin-Like Growth Factor

Determination of IGF-I gives an indirect indication of GH concentration. Increased IGF-I concentrations develop in acromegalic dogs and, seemingly, in acromegalic cats; however, increased IGF-I concentrations may also be found in diabetic cats without evidence of acromegaly. A validated assay is available at the Endocrine Diagnostic Laboratory of Michigan State University (telephone: 517-353-0621, website: www.ahdl.msu.edu).



Treatment of Progesterone-Induced Acromegaly


Treat progesterone-induced acromegaly by ovariohysterectomy or discontinuation of progestogen drugs. The soft tissue overgrowth and respiratory stridor resolve; however, the skeletal changes persist. The insulin requirement for GH-induced diabetes mellitus also declines, but the reversibility of the diabetes depends on the insulin reserve of the pancreatic beta islet cells.



Treatment of Growth Hormone-Secreting Pituitary Tumors


Manage these tumors by surgery, radiation, or drug therapy.



Surgery


• Because surgical excision of the tumor probably necessitates a hypophysectomy, expect deficiencies of pituitary hormones postoperatively.

• Before surgery, precisely localize the pituitary tumor by CT or MRI because neoplastic extension into the hypothalamus precludes surgery.

• Trans-sphenoidal cryotherapy of a pituitary tumor in an acromegalic cat has been performed.

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Aug 27, 2016 | Posted by in SMALL ANIMAL | Comments Off on Diseases of the Hypothalamus and Pituitary

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