Hypothalamus & Neuroendocrine Flashcards
By the end of your study, you should be able to recognize the anatomical boundaries of the hypothalamus and its various nuclei, identify their function with respect to the autonomic nervous system and the pituitary gland. You should be able to recognize that lesions of the hypothalamus and pituitary are often combined and produce effects through some form of endocrine dysfunction and/or compression of the optic chiasm.
I present this diagram of hypothalamic anatomy as a supplement to the figures in your textbook.
In this course you will not be asked to identify which releasing factor or hormone is made in which hypothalamic nucleus but you are expected to know the function of these releasing factors and hormones.
You are also expected to know the general structure/function of the hypothalamus as it relates to the regulation of body temperature, eating, water balance, and circadian rhythms.
What follows is selected commentary on the clinical presentation of some lesions that affect the hypothalamus and pituitary gland.
Because the anatomical structure-function of the hypothalamus and pituitary gland are so tightly linked, it is sometimes difficult to distinguish which of the two structures is responsible for an endocrine-related disorder.
Lesions of either structure may cause increased or decreased function of the hypothalamic/pituitary system, depending upon the nature of the lesion.
Disorders of the hypothalamus/pituitary are most frequently the result of a tumorous growth that will be discussed below. Vascular events, such as pituitary apoplexy, local infection, inflammation, for example with neuro-sarcoid, may also cause endocrine dysfunction and other neurological signs and symptoms due to disruption of nearby structures.
I present this slide as a supplement to the figures in Krebs et al. because I believe it presents a clear pictorial view of pituitary hormones and their function.
This Netter figure nicely summarizes the relationship between the hypothalamus and the autonomic nervous system.
Note that the parasympathetic pathways originate in hypothalamic neurons found anteriorly in the hypothalamus, shown in blue, and the sympathetic pathways originate in neurons lying more posteriorly, shown in red.
Adenomas of the pituitary gland are usually benign neoplasms that present with endocrine hyperactivity depending on the proliferating cell type and hormone being secreted.
Other adenomas do not secrete hormones but produce their clinical effects by expansion and blockade of normal pituitary function and by pressure on nearby structures such as the optic chiasm.
The size of the adenoma is important for determining the therapeutic approach. Why?
Microadenomas, those less than10 mm in size may respond to medical or radiation therapy while
macroadenomas, tumors greater than 10 mm, frequently require surgical removal.
Approximately 80% of tumors in the pituitary region are:
pituitary adenomas, 10% are craniopharyngiomas and 10% either meningiomas or pituicytomas.
What are Craniopharyngiomas?
Rare tumors that derive from remnants of Rathke’s pouch along a line from the nasopharynx to the diencephalon.
They are located either in the intrasellar space or just above in the suprasellar area.
How do craniopharyngiomas present?
Roughly half of cranipharyngiomas present clinically during childhood or adolescence and the other half show themselves after the second or third decade of life. Because of their mass effect, craniopharyngiomas usually cause growth retardation in children due to interference with growth hormone.
Craniopahryngiomas may also present with other pituitary hormonal deficiencies, diabetes insipidus being the most common.
In adults, visual field defects are usually the presenting sign due to compression of the optic chiasm and/or optic nerves. If the craniopharyngioma splays the fornices just before they dive into the mamillary bodies, the limbic system may be affected and memory problems may ensue.
What are meningiomas?
Meningiomas are benign tumors derived from meningeal membranes. They may arise anywhere within the calvaria and those that occur near the sella cause visual impairment and hormonal deficiencies. Pituicytomas are rare, low-grade gliomas derived from the pituicytes of the posterior pituitary gland. They present as a mass lesion similarly to a meningioma. They are non-secreting tumors.
Prolactinomas, when small, cause galactorrhea, amenorrhea, hypogonadism and erectile dysfunction. When they enlarge beyond 1 cm, they can additionally cause headache and visual field defects due to compression of the optic chiasm. Panhypopituitarism is also possible.
Adenomas that secrete growth hormone cause gigantism and acromegaly.
ACTH secreting tumors cause Cushing’s disease. T
hyrotroph adenomas may secrete TSH and present with hyperthyroidism, or they may be nonsecreting and present as a pituitary mass.
Gonadotroph adenomas are usually nonsecreting tumors that present as macroadenomas but they may cause infertility.
The secreting pituitary adenomas are usually detected as microadenomas because they create obvious clinical endocrine symptoms. For example, a patient with an ACTH secreting adenoma will present with Cushingoid signs way before the tumor ever reaches proportions large enough to compress visual pathways.
The prolactin secreting microadenomas are best treated with dopamine agonists, such as bromocriptine, since dopamine serves as the natural prolactin inhibiting factor. Even large prolactinomas respond well to dopamine agonist therapy.
The non-secreting adenomas remain clinical silent until their size encroaches upon other structures, usually the optic chiasm and/or optic nerves.
This prolactin secreting tumor reached huge proportions before therapy was started.
Before prolactinomas were found to be sensitive to dopamine agonists, they used to be treated with a combined excision procedure, one from below via the nasopharynx and a second from above via a fronto-temporal craniotomy. Needless to say, morbidity could be considerable even when the surgery went well.
These days, the tumor is recognized as a prolactinoma by galactorrhea, a markedly elevated serum prolactin and by its response to empirical treatment with a dopamine agonist such as bromocriptine. Dopamine agonist therapy can be quite effective as shown above and carries far less risk than surgery
Take a moment to figure out what kind of pituitary abnormality is on display. Excessive secretion of Growth hormone, ACTH and TSH is correct.
