Hypothalamic Hypopituitarism Following Cranial Irradiation for Nasopharyngeal Carcinoma

Abstract

Eight patients, one male and seven females, with no pre-existing hypothalamic-pituitary disease, who developed symptoms of hypopituitarism following cranial irradiation for nasopharyngeal carcinoma were studied 5 years or more after radiotherapy. All were GH deficient. Four of the patients with no GH response during insulin tolerance tests (ITT) showed increased GH in response to synthetic human growth hormone releasing factor (GRF-44). Four patients had impaired cortisol responses to ITT, and gradual but diminished cortisol responses to ovine corticotrophin releasing factor (CRF-41). There was no significant difference between mean peak increments in response to ITT and those in response to CRF-41. TSH responses to TRH were delayed in five and absent in two patients; four of these had low free T4 index. Prolactin was raised in all seven women and increased further in response to TRH. Two patients had impaired gonadotrophin responses to LHRH. None of the patients had clinical or biochemical evidence of diabetes insipidus. These data suggest that post-irradiation hypopituitarism in these patients results from radiation damage to the hypothalamus leading to varying degrees of deficiency of the hypothalamic releasing or inhibitory factors.

Effect of Radiation on the Human Reproductive System

“…This is further supported by the finding of galactorrhea and hyperprolactinemia in some of these patients (1).…”

“…In general, lethally irradiated cells die during division. Differentiating spermatogonia are very radiosensitive, and after doses as low as 1 Gy both their numbers and that oftheir daughter cells, the preleptotene spermatocytes, are severely reduced (27). The doses of irradiation required to kill spermatocytes are higher than for spermatogonia (2-3 Gy results in an inability to complete maturation division, with a resultant decrease in spermatid numbers).…”

Hypogonadism in men with erectile dysfunction may be related to a host of chronic illnesses

“…It has been well established that acute illness will cause hypogonadotropic, or secondary, hypogonadism. 36 This has been shown in a variety of clinical situations, including acute burns, 37 ethanol abuse, 38 presence and treatment of carcinoma, 39 or head trauma. 40 Psychological stresses have also been shown to cause secondary hypogonadism, as shown by Kreuz et al, 41 in the study of military officer candidate training, 42 or in combat situations under the threat of attack.…”

Thyroid Sequelae of Pediatric Cancer Therapy

“…Direct neuronal injury is the most likely cause, but there may also be secondary contributions from vascular damage and reduced blood flow [69, 71]. Although the hypothalamus is believed to be more susceptible to radiation injury [72], and thus hypothalamic dysfunction considered to be the primary cause of hypopituitarism [36, 69, 73], there are data suggesting that the pituitary gland is also vulnerable, especially after higher radiation doses [72, 74]. …”

“…Often, the downward trend in T4 levels can help to alert the clinician to the diagnosis [72, 74, 124]. Historically, TRH was commonly used in diagnostic testing [23, 36, 37, 45, 69, 70, 73, 77], but TRH is no longer readily available nor advised [124]. If the diagnosis of central hypothyroidism is entertained, it would be prudent to screen for other pituitary hormone deficiencies, if not already done.…”