Hypothalamus Anatomy and Function

• The hypothalamus and pituitary control the endocrine system and can cause visual deficits due to their anatomical relations.
• A 50-year-old woman experienced worsening vision, menstrual irregularity, and infertility; the cause was a pituitary lesion compressing her optic chiasm.
• The hypothalamus and pituitary use both synaptic transmission and soluble humoral factors for communication.
• The pituitary and hypothalamus link the neural and endocrine systems.
• The hypothalamus regulates homeostasis and is nicknamed the "homeostatic head ganglion."
• The hypothalamus maintains homeostasis by influencing:
  • Homeostatic mechanisms like hunger, thirst, and sleep cycles
  • Endocrine control via the pituitary
  • Autonomic control
  • Limbic mechanisms (HEAL: Homeostasis, Emotion, Autonomic, Limbic)
• The pituitary is derived from two embryological pouches.
• The anterior pituitary (adenohypophysis) forms from Rathke's pouch.
• The posterior pituitary (neurohypophysis) forms from the developing ventricular system.
• The anterior pituitary contains glandular cells that secrete hormones into the circulation, controlled by the hypothalamus via a vascular portal system.
• The posterior pituitary contains axons and terminals of hypothalamic neurons, secreting oxytocin and vasopressin into the circulation.
• The hypothalamus is part of the diencephalon, located under the thalamus.
• The hypothalamus forms the walls and floor of the inferior third ventricle.
• The hypothalamic sulcus separates the hypothalamus from the thalamus.
• The tuber cinereum and mammillary bodies are visible on the ventral surface of the brain, posterior to the optic chiasm.
• The infundibulum arises from the tuber cinereum and continues as the pituitary stalk.
• The anterior infundibulum is slightly elevated and called the median eminence; it is where hypothalamic neurons release regulating factors to the anterior pituitary.
• The pituitary gland lies within the pituitary fossa, bounded by the anterior and posterior clinoid processes, forming the sella turcica.
• The sphenoid sinus lies beneath the sella turcica and allows transsphenoidal surgical access to the pituitary fossa.

Important Hypothalamic Nuclei and Pathways

• Hypothalamic nuclei specialize in homeostatic, autonomic, and limbic functions and are divided into four regions (anterior to posterior) and three areas (medial to lateral).
• The periventricular nucleus is a thin layer of cells closest to the third ventricle.
• The fornix divides the hypothalamus into medial and lateral hypothalamic areas.
• The lateral hypothalamic area contains the lateral hypothalamic nucleus and the medial forebrain bundle (MFB).
• The medial hypothalamic area consists of several nuclei divided into four regions (anterior to posterior).
• The preoptic area is derived from the telencephalon but functions as part of the hypothalamus.
• The anterior hypothalamic (supraoptic) region includes the anterior hypothalamic, supraoptic, paraventricular, and suprachiasmatic nuclei.
• The middle hypothalamic (tuberal) region includes the arcuate, ventromedial, and dorsomedial nuclei.
• The posterior hypothalamic (mammillary) region includes the medial, intermediate, and lateral mammillary nuclei, and the posterior hypothalamic nucleus.
• The paraventricular nucleus, dorsomedial hypothalamic nucleus, and lateral and posterior hypothalamus have descending projections influencing sympathetic and parasympathetic nervous systems.
• Inputs to the hypothalamus that regulate autonomic function: synaptic and humoral sources, amygdala, and limbic cortex regions (orbital frontal, insular, anterior cingulate, and temporal cortices).

Hypothalamic-Limbic Pathways

• The subiculum of the hippocampal formation projects to the mammillary bodies via the fornix.
• The mammillary bodies project to the anterior thalamic via the mammillothalamic tract, which in turn projects to limbic cortex in the cingulate gyrus.
• The amygdala has reciprocal connections with the hypothalamus via the stria terminalis and the ventral amygdalofugal pathway.
• Limbic-hypothalamic interconnections are tied to emotional and homeostatic pathways.
• Hypothalamic hamartomas can cause laughing episodes (gelastic epilepsy), emotional disturbances, and cognitive impairment and, at times, precocious puberty.

Other Regionalized Functions of the Hypothalamus

• The suprachiasmatic nucleus in the anterior hypothalamus regulates circadian rhythms and receives inputs from retinal ganglion cells containing melanopsin via the retinohypothalamic tract.
• GABAergic neurons in the ventral lateral preoptic area (VLPO) contribute to non-REM sleep: they inhibit posterior hypothalamic arousal systems.
• Lesions of the anterior hypothalamus, including the VLPO, tend to cause insomnia.
• Lesions of the posterior hypothalamus tend to cause hypersomnia.
• The lateral hypothalamus is important in appetite; lesions cause decreased body weight.
• Low levels of Leptin, which binds to Ob receptors in the hypothalamus, lead to increased appetite/obesity.
• High levels of Ghrelin, which is produced by gastric mucosal cells, leads to stimulated appetite.

Hypothalamus and Temperature Control

• Activation of osmoreceptors in the anterior hypothalamus results in thirst.
• Decreased water intake results from the thirst response being impacted when lesions are made in the lateral hypothalamus.
• Increased body temperature and heat dissipation detected by anterior hypothalamus.
• Anterior hypothalamic lesions can cause hyperthermia.
• The posterior hypothalamus functions to conserve heat.
• Bilateral posterior hypothalamus lesions cause poikilothermia.
• Production of oxytocin in the hypothalamus and released in the posterior pituitary has been tied to increased nurturing behaviors.
• Sexual development and differentiation regulated by the hypothalamus using neural and endocrine interplay.

Endocrine Functions of the Pituitary and Hypothalamus

• The anterior pituitary produces:
  • Adrenocorticotropic hormone (ACTH)
  • Growth hormone (GH)
  • Prolactin
  • Thyroid-stimulating hormone (TSH)
  • Luteinizing hormone (LH)
  • Follicle-stimulating hormone (FSH)
• The intermediate lobe produces pro-opiomelanocortin (POMC) and melanocyte-stimulating hormone (MSH), and has little clinical significance.
• The posterior pituitary releases:
  • Oxytocin
  • Vasopressin (arginine vasopressin (AVP) or antidiuretic hormone (ADH))
• Release of anterior pituitary hormones is controlled by hypothalamic neurons through the hypophysial portal system.
• Neurons lying adjacent to the third ventricle in several hypothalamic nuclei project to the median eminence, secreting inhibitory and releasing factors.
• These nuclei include the arcuate nucleus, periventricular nucleus, medial preoptic nucleus, and medial parvocellular portions of the paraventricular nucleus.
• Vasopressin produced by the supraoptic nucleus and oxytocin by the paraventricular nucleus.
• ACTH stimulates the adrenal cortex to produce corticosteroid hormones.
• TSH stimulates the thyroid gland to produce thyroxine (T4) and triiodothyronine (T3).
• Growth hormone causes the liver, kidneys, and other organs to produce somatomedins or insulin-like growth factors (IGF).
• Prolactin causes the mammillary glands to produce milk.
• LH and FSH regulate ovarian hormones responsible for the menstrual cycle and oogenesis in females, and testicular hormones and spermatogenesis in males.
• Oxytocin causes contractions of smooth muscle in the breast for milk letdown and contractions of the uterus during labor.
• Vasopressin, or ADH, participates in osmotic regulation by promoting water retention by the kidneys, allowing concentration of the urine.
• The release of hormones in the hypothalamic-pituitary axis is regulated by feedback loops.
• Chronic steroids can lead to adrenals atrophy and a dependency to them for body regulation.

Pituitary Adenoma and Disorders

• Pituitary adenoma is a slow-growing tumor arising from glandular epithelial cells in the anterior pituitary, accounting for 17% of intracranial neoplasms in adults.
• Hormone secretion by pituitary adenomas is often in excess of normal levels and is not under normal hypothalamic control.
• Nonfunctioning adenomas often grow larger before causing symptoms and commonly induce headaches.
• Tumors of the pituitary can compress the optic chiasm and cause visual disturbances, including bitemporal hemianopia.
• Prolactin is the most commonly secreted hormone in pituitary adenomas (50% of all pituitary adenomas).
• Treatment options for pituitary adenomas: medication, surgery, and radiotherapy.
• Treatment of non-prolactin-secreting tumors is typically done by surgery.
• The somatostatin analogue octreotide has shown promising results in growth hormone-secreting tumors.
• Transsphenoidal approaches are taken to remove pituitary tumors through the nasal cavity.
• Gamma knife radiotherapy is mainly used for cases that fail to respond to surgery.
• Prolactin-secreting adenomas typically cause amenorrhea in women, hypogonadism in men, and galactorrhea, infertility, hair loss, and decreased libido in both sexes.
• Elevated prolactin levels (>150 micrograms per liter in nonpregnant patients) are virtually diagnostic of pituitary adenoma.
• Growth hormone-secreting adenomas in adults cause acromegaly and gigantism in children.
• Other common problems in patients with growth hormone excess includes; carpal tunnel syndrome, arthritis, infertility, hypertension, and diabetes.
• ACTH-secreting adenomas cause Cushing's disease.
• Endogenous Cushing's syndrome is caused by primary adrenal adenomas or adenocarcinomas.
• When suspecting ACTH-producing tumors, dexamethasone suppression tests, CRH and MRI can be useful tests. Petrosal sinus sampling is used to confirm that excess ACTH is from a pituitary source.

Hyperthyroidism/Hypothyroidism

• TSH-secreting adenomas cause hyperthyroidism: nervousness, insomnia, weight loss, tremor, excessive sweating, heat sensitivity, increased sympathetic output, and frequent bowel movements.
• TSH levels are completely suppressed if the hyperthyroidism is caused by primary thyroid disorders.
• Hypothyroidism manifestations: lethargy, weight gain, cold intolerance, smooth/dry skin, hair loss, depression, and constipation.
• LH- or FSH-secreting adenomas can reach a relatively large size before being detected; can produce either high or low levels of hormones.
• A variety of lesions occur in the sellar and suprasellar region, including: craniopharyngioma, aneurysms, meningioma, optic glioma, hypothalamic glioma, cordoma etc.

Diabetes Insipidus and SIADH

• Characterized by high levels of dilute urine production (DI)
  • Neurogenic DI - caused by ADH deficiency -Nephrogenic DI - caused by insensitivity of kidneys to ADH
• DI Symptoms: Thirst, polydipsia, and polyuria.
• SIADH: Characterized by excess ADH production creating a low sodium serum and elevated urine osmolality.
  • Severe levels can cause lethargy, coma and seizures.

Panhypopituitarism

• Deficiency of multiple pituitary hormones, in several conditions of the pituitary and hypothalamic regions; however, primary pituitary tumors and their treatment are the most common.
  • ACTH deficiency causes hypocortisolism
  • TSH deficiency causes hypothyroidism
  • ADH deficiency causes diabetes insipidus
  • LH and FSH deficiencies cause hypogonadism
  • GH deficiency in children abnormally short stature etc.
• Primary pituitary tumors and their treatment are the most common cause; other lesions include: non functioning tumors, meningioma, craniopharyngioma, hypothalamic tumors and more.
• Panhypopituitarism is treated by hormones from; daily administered steroids to treat ACTH insufficiency, synthoid hormones to treat HYPOthyroidism etc.

Questions about the hypothalamus, its nuclei, and connections to the pituitary gland, autonomic nervous system, and limbic system. Focus on the paraventricular nucleus, arcuate nucleus, and circadian rhythms.