Smell, Taste, Head Trauma, and Hypopituitarism

Although the recent clinical review by Benvenga et al. (1) highlighted the relationship between head trauma and hypopituitarism, less well known but equally important clinically are the putative relationships among head trauma, hypopituitarism, and loss of smell. While endocrinologists focus on etiologic relationships that provoke hormonal dysfunction, it may also be relevant for endocrinologists to focus on hormonal interactions that may have neurological or other metabolic consequences. Most physicians attribute loss of smell acuity following head trauma to an anatomical defect caused by severing the fila olfactoria of the cribriform plate due to direct or indirect effects of the trauma. However, in the vast majority of patients this type of injury does not occur. If this were the case, then retrograde degeneration of olfactory tracts would occur with diminution of olfactory nerve and tract volume and subsequent degenerative changes in rectus gyrus and other olfactory-related areas of the brain. Such changes do not occur. Our measurements of olfactory nerves and tracts in patients with head trauma, many several years after the injury, demonstrated normal area (2, 3) despite measured loss of smell of severe degree (4, 5). Indeed, while some of these patients exhibit Type I hyposmia (loss of ability to recognize vapors at any concentration) or anosmia (loss of ability to detect or recognize vapors at any concentration), most exhibit Type II hyposmia (decreased detection and recognition thresholds for various vapors; Ref. 5); this latter, more common defect entails an intact anatomical system in which olfactory acuity is decreased but present, to some degree (5). As reviewed by Benvenga et al. (1), patients with head trauma may exhibit hypopituitarism; they may also exhibit decreased ability to recognize odors, as we have demonstrated by use of brain functional magnetic imaging in which decreased brain activation to odors in patients with head injury has been measured quantitatively and demonstrated visually (6, 7). These observations confirmed the acknowledged loss of smell in these patients, but this loss was related directly to their inability to process olfactory information (i.e. recognize odors). While we have not studied patients with both head trauma and hypopituitarism, there is an important perceptual duality in these patients that provides additional but initially confusing information about the nature of their hypopituitarism and head injury as related to their hyposmia. It is well known that patients with hypopituitarism who have hypoadrenal function exhibit increased ability to detect odors (8) and tastes (8A ) but decreased ability to recognize odors or tastes (9–11). This duality is usually interpreted by both patient and clinician as loss of sensory function because interference with recognition ability is the clinically overriding symptom. Because head trauma and its putative cause of anatomical injury have been associated with loss of ability to recognize odors, it would be easy to confuse etiology of loss with either hormonal or anatomical considerations, and such has indeed occurred. Thus, since our data indicate that anatomical effects are not the primary cause of smell loss in this condition, the main mechanism of recognition loss may be due to changes in secretion of hormones and other growth factors initiated by the trauma. The mechanistic convergence of these two phenomena generates the hormonal nexus for these two events. One role of lack of hormonal secretion in head injury as related to smell loss lies in the hypopituitarism, directly related to the effects of hormonal lack on smell function (8, 10–12). Thus, with hypothyroidism (12, 13) or hypoadrenal function per se, taste and smell recognition are impaired. The other role of lack of hormonal secretion in head injury may relate to actions of hormones and growth factors on stem cells of taste buds and olfactory epithelium because they induce maturation and differentiation of the elegant repertoire of cellular components that comprise these two sense organs (14–16). In this complex system, while many factors may be involved with induction of hyposmia, the complex interactions between endocrine status, head trauma, and ability to recognize tastes and odors are important for patient, endocrinologist, and neurologist to consider. Replacement hormone treatment may not only correct the symptoms of hypopituitarism but may also correct those of the smell (8) and taste loss (8A ) in these patients. These interactions are as important to emphasize as are those emphasized by Benvenga et al. (1) because as many as 60% of patients with head injury may experience loss of smell (5), albeit many fewer may experience hypopituitarism.