xRead - Olfactory Disorders (September 2023)

20426984, 2022, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/alr.22929, Wiley Online Library on [04/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

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PATEL et al.

3 Endocrine related There are multiple endocrine disorders that can potentially affect olfactory mechanisms. Endocrine dysfunction can produce changes within the mucosal lining of the nose, the olfactory neural pathway, or the olfactory repair mech anisms. Disorders involving the hypothalamus can include hypothalamic dysfunction, which can lead to primary amenorrhoea and occasionally anosmia. In the same vein, patients with Froehlich syndrome, or adiposogenital dys trophy, experience smell deviations following damage to the arcuate nucleus and ventromedial nuclei of the hypothalamus. 459 Subsequent lack of hormone secretion from the anterior pituitary causes delay in normal puberty and its associated features. 459,460 The pituitary gland itself, while crucial in various home ostatic functions, also plays an important role in olfac tion. Endocrinologic manifestations of Cushing syndrome can include inappropriate antidiuretic hormone secretion, catecholamine secretion, hyperprolactinemia, and adreno corticotropic hormone secretion. There is the potential for the subsequent symptoms associated with these derange ments to include anosmia. 460 On the other hand, patients with adrenocortical insufficiency (at times secondary to a pituitary cause), also called Addison disease, have a decreased ability to recognize odors. This is primarily related to the effects of hormonal reduction on smell function, but also attributed to the actions of those hor mones on stem cells in the OE, which induce maturation and differentiation. 461,462 Acromegaly and gigantism, sec ondary to hypersecretion of growth hormone and, in turn, insulinlike growth factor 1, are chronic, progressive, mul tisystem diseases. Part of the spectrum of clinical features can include hyposmia or anosmia. It is also worth noting that patients with de Morsier syndrome, septo-optic dys plasia, can have symptoms of anosmia secondary to pitu itary variability. 459,463 Patients with hypothyroidism have similar impairments in smell recognition secondary to deficient hormonal effects on the olfactory organ, and, by treating primary hypothyroidism, olfactory ability can improve. 464,471 Other deviations resulting in olfactory variations can affect the OB and receptor environment. Kallman syn drome, otherwise known as hypogandotrophic hypogo nadism, is an X-linked neuronal migrational disorder that causes anosmia secondary to aplasia of the OB. 465,466 Turner syndrome shares some parallel symptomology to Kallman syndrome, including OD, but with markedly dif ferent etiology. 467 As noted in the section above, patients with Sjögren syndrome can experience excessive dryness of the nasal mucosa, as evidenced in atrophic rhini tis, with resultant OD secondary to loss of moisture within the receptor environment. This ultimately leads to

diminished chemoreception and transduction and effects on the hypothalamic-pituitary-adrenal axis. 398,459 Inter estingly, normal changes during pregnancy can result in notable alterations in perception of smells secondary to hormonal changes in the mucosa. These changes can be responsible or manifest as either hyperosmia, hyposmia, or anosmia, with most cases only temporary until the time of delivery. 468 Finally, a combination of the secondary neurodegener ation and microvascular disease associated with diabetes mellitus (DM) results in a significant proportion of patients with DM experiencing diminished smell sensation. 469,470 Although this can be gradual in onset, and often unde tected, there seems to be no correlation between DM dura tion and prevalence of OD. Underlying endocrine disorders can affect the functionality of the olfactory system. Aggregate grade of evidence : C (Level 3: four studies; Level 4: four studies; Level 5: three studies). 4 Renal failure Our systematic literature review identified that patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD) commonly experience olfac tory impairment—a finding consistent with narrative reviews by Raff et al, 472 Landis et al, 473 and recently by Robles-Osorio et al. 474 Controversies persist, regarding which aspects of olfaction are affected in renal patients, or whether undergoing dialysis alleviates olfactory impairment. Kidney disease affects odor identification capacity, 472,473,475 and OD correlates with the severity of kidney disease. 476,477 Odor discrimination is also diminished in renal patients. 475,478–480 Results concerning odor detection threshold in these patients are conflict ing, describing either no change 475,481,482 or significant impairment. 477 Most early studies, however, had sample size limitations. 473,478–480 Recently, Koseoglu et al 483 reported impaired odor identification, discrimination, and threshold in non-DM patients with renal failure versus control participants. This study found that ≈ 80% of renal patients experience olfac tory impairment and suggested that dialysis may improve olfaction. In the largest study to date (n = 161), Nigwekar et al 484 reported odor identification impairment in most patients withCKD( ≈ 70%) and ESKD ( ≈ 90%). Detection threshold was comparable between patients with CKD and control participants, but higher in patients with ESKD. Proposed explanations for olfactory impairment in renal patients 477 range from accumulation of uremic toxins impairing olfaction 485,486 or inducing polyneuropathy, 487