CAUSES	FEATURES
Graves disease	Hyperthyroidism, goiter, ophthalmopathy, pretibial myxedema; may remit
Toxic goiter	A result of hypersecretion of thyroid-stimulating hormone, but does not usually remit
Thyroiditis	Hyperthyroidism during acute phase; may “burn out”
Related to drugs	Lithium and amiodarone

Figure 15.1-1 The “thyroid stare.”
A, The patient appears startled. This finding is the result of eyelid retraction likely caused by sympathetic overactivation; it does not mean that Graves disease is present. B, Hyperthyroidism is much more common in females.

Figure 15.1-2 Graves ophthalmopathy.
A, Corneal injection and proptosis. Extraocular muscle weakness on left lateral gaze (B), right lateral gaze (C), and upward gaze (D). The patient reported double vision.

Figure 15.1-3 Polysomnogram of sweat artifact.
Note the high-amplitude swings in all the electroencephalogram channels in synchrony with breathing. This patient had night sweats. Hyperthyroidism was first suspected from this finding and from the newly noted atrial fibrillation. Top and bottom windows are 30-second epochs.

Figure 15.1-4 Atrial fibrillation.
The electromyogram panel shows a 15-second epoch. This is the same patient as shown in Figure 15.1-3.

Hypothyroidism

The clinical features of hypothyroidism are those related to a hypometabolic state and those related to the effect on the cardiovascular and respiratory systems; these are described in Boxes 15.1-3 through 15.1-5, and Figures 15.1-5 to 15.1-8. Hypothyroidism is a risk factor for the development of sleep apnea and is much more common in women than in men. In particular, patients who have been diagnosed with Hashimoto thyroiditis are at risk.

Box 15.1-3 Symptoms of Hypothyroidism

• Weight gain

• Cold intolerance

• Changes in skin and hair (drier, coarser, loss)

• Macroglossia

• Hoarse voice

• Puffiness around eyes

• Constipation

• Changes in personality

Box 15.1-4 Sleep Findings in Hypothyroidism

• Obstructive sleep apnea

• Potential respiratory failure

• Excessive sleepiness

• Bradycardia

Box 15.1-5 Causes of Hypothyroidism

• Primary (may occur after “burned out” thyroiditis)

• Secondary to radiotherapy or medical therapy of thyroid disease

• Iodine deficiency

• Drug induced (lithium, amiodarone)

Figure 15.1-5 “Burned out” Graves disease.
A, This patient, who had been treated for Graves disease, developed severe hypothyroidism with obesity and sleepiness and was found to have severe obstructive sleep apnea. Note the conjunctival injection and the droopy lids. B, When the patient is focused and alert, the eye signs of proptosis and the asymmetry of eye movements become apparent. C, The characteristic bulging eyes (exophthalmos) of Graves disease.

Figure 15.1-6 This figure shows the development of hypothyroidism over time.
The patient developed coarse facial features, puffy eyes, and cold intolerance. Note that the patient is wearing a scarf indoors.

Figure 15.1-7 Features of hypothyroidism.
A, Puffy eyes. B, Fullness in the neck and a scar from thyroid surgery. C, A large tongue (macroglossia) fills up the mouth, impinging on the oropharyngeal airway. D, Brittle, sparse hair, receding hairline, and loss of hair in eyebrows.

Figure 15.1-8 Features of hypothyroidism.
This young woman had sleep apnea related to an enlarged thyroid gland. Note the fullness in her neck on lateral (A) and anterior (B) views.

Thyroid Mass Lesions

These lesions are detected either by inspection or palpation. In patients with thyroiditis, the gland may be tender. Refer to Boxes 15.1-6 and 15.1-7 and Figure 15.1-9.

Box 15.1-6 Types of Thyroid Mass Lesions

• Idiopathic goiter

• Secondary to radiotherapy or medical therapy of thyroid disease

• Iodine deficiency

• Tumors

Box 15.1-7 Sleep Findings with Thyroid Mass Lesions

• Snoring

• Apnea

• Stridor

Figure 15.1-9 Severe sleep apnea with stridor.
This patient previously had a radical neck dissection for thyroid cancer that had invaded the trachea, and the sternocleidomastoid muscles had been removed.

Selected Readings

Bozkurt, NC, Karbek, B, Cakal, E, et al. The association between severity of obstructive sleep apnea and prevalence of Hashimoto’s thyroiditis. Endocr J. 2012; 59(11):981–988.

Misiolek, M, Marek, B, Namyslowski, G, et al. Sleep apnea syndrome and snoring in patients with hypothyroidism with relation to overweight. J Physiol Pharmacol. 2007; 58(Suppl 1):77–85.

Neal, JM, Yuhico, RJ. “Myxedema madness” associated with newly diagnosed hypothyroidism and obstructive sleep apnea. J Clin Sleep Med. 2012; 8(6):717–718.

Resta, O, Carratù, P, Carpagnano, GE, et al. Influence of subclinical hypothyroidism and T4 treatment on the prevalence and severity of obstructive sleep apnoea syndrome (OSAS). J Endocrinol Invest. 2005; 28(10):893–898.

Resta, O, Pannacciulli, N, Di Gioia, G, et al. High prevalence of previously unknown subclinical hypothyroidism in obese patients referred to a sleep clinic for sleep disordered breathing. Nutr Metab Cardiovasc Dis. 2004; 14(5):248–253.

15.2

Diseases of the Pituitary Gland

Meir H. Kryger

Anatomy

The pituitary gland is located near several structures that are involved in the regulation of sleep (Fig. 15.2-1). Above the pituitary is the hypothalamus, which contains centers involved in the regulation of sleep and temperature, and the suprachiasmatic nucleus, which is the master controller of the circadian rhythm.

Figure 15.2-1 An enlarging pituitary tumor compresses structures in and around the pituitary gland.
These structures have an effect on the regulation and timing of sleep.

Thus any space-occupying disease that involves the pituitary or nearby structures, such as ademomas and crainiopharyngiomas, can affect sleep and may cause sleepiness, insomnia, and temperature dysregulation. In hormone-secreting tumors, the impact on sleep may be related to the effects of the hormone. The best known of the pituitary diseases that affect sleep are those that result in hypersecretion of growth hormone.

Growth Hormone Hypersecretion

Pathophysiology

Hypersecretion of growth hormone can result in metabolic abnormalities and anatomic changes of skeletal and soft tissue structures that may result in obstructive sleep apnea (OSA). The most common cause of excess secretion of growth hormone is a pituitary tumor (see Fig. 15.2-1). The clinical presentation (Box 15.2-1) is related to the age of the patient, the local effects of the enlarging tumor on the structures in and around the pituitary gland, and the resulting metabolic and anatomic changes. When these result in orofacial changes (Figs. 15.2-2 and 15.2-3), the patient may develop OSA.

Box 15.2-1 Clinical Features of Acromegaly

Sleep apnea syndrome

Compression caused by pituitary adenoma

• Visual field defects

• Hypopituitarism, hyperprolactinemia, hypogonadism, galactorrhea

Direct growth hormone consequences

• Impaired glucose tolerance and diabetes mellitus

Soft tissue abnormalities (see Figs. 15.2-3 and 15.2-5)

• Myopathy

• Soft tissue enlargement of nose, tongue, larynx, visceral organs

• Thick skin

Bony changes (see Figs. 15.2-4, 15.2-6, and 15.2-7)

• Enlargement of hands and feet

• Osteoarthritis

• Prognathia and increased interdental spacing

Figure 15.2-2 Acromegaly evolved slowly in this patient, who developed sleep apnea.
These photographs show the changes in facial features over many years. Between ages 33 and 38, a marked coarsening of the features occurs. Note the distance between the eyebrows and that the eyes increased in size because of the bossing of the forehead. Sleep apnea symptoms also developed slowly.

Figure 15.2-3 Acromegaly.
A, This is the same patient as shown in Figure 15.2-2, now in her 60s. A large jaw and nose, frontal bossing, coarse facial features, thick skin, and deep facial creases are apparent. The sleep apnea is believed to be due to the anatomic changes, including the enlarged tongue (B) and the abnormal jaw structure. This patient has severe obstructive sleep apnea and has been on nasal continuous positive airway for several years. C, Examination of the lower jaw and dental structures reveals increased space between the teeth caused by enlargement of the jaw. D, Note the frontal bossing and the healed scar from surgery to treat the pituitary tumor. In some patients, the lower jaw juts forward (prognathism). E, One of the first signs the patient noted was enlargement of her hands.