algia, loss of appetite and nausea.

No past history mEq/L), azotemia (urea = 97 mg/dl, creatinine

of tuberculosis, diabetes mellitus, thyroid disor- 1.7), hypertriglyceridemia (triglycerides 400 mg/
Addison’s disease and autoimmune ders, alcoholic liver disease, drug consumption or dl) and elevated serum transaminases (glutamic

thyroiditis with hypothyroidism any other comorbid illness was identified. There
was no relevant family history.
oxaloacetic transaminase (GOT) 40 UI/L, glu-
tamic-pyruvic transaminase (GPT) 46 UI/L).
On clinical examination, the patient was apy-
– A case report retic, with blood pressure of 90/50 mmHg, pulse
of 90 bpm and generalized skin hyperpigmenta-
tion (Figure 1.), more accentuated on the elbows
Breabăn Iulia (Figure 2.) and palmar creases (Figure 3.).
Resident in gastroenterology

Stefan Andreea Maria

Resident in gastroenterology

Abstract. Addison’s disease is a relatively rare endocrine condition with an annual incidence of 4.7-
6.2 per million people in Western populations [1], most frequently (about 80% of cases) of autoimmune
etiology [2]. As part of a polyglandular autoimmune syndrome, it can also associate with autoimmune
thyroiditis, diabetes mellitus and mucocutaneous candidiasis.
We herein report the case of a 30-year-old man with Addison’s disease and autoimmune thyroiditis
with hypothyroidism, with a history of approximately one year of asthenia, unintentional weight loss, my- Figure 1. Hyperpigmentation of the skin Figure 3. Hyperpigmentation of
algia and nausea, general melanoderma, chronic hepatocytolysis syndrome and mild elevated creatinine. the palmar creases
Keywords: Addison’s disease, autoimmune thyroiditis with hypothyroidism, polyglandular autoim-
mune syndrome
Based on clinical and laboratory findings, Ad­­
di­son’s disease was suspected as the main diag-
nosis, therefore cortisol and adrenocorticotropic
Introduction into the polyglandular autoimmune syndrome hormone (ACTH) were dosed. Up to the mo-
Addison’s disease is a rare endocrine disorder [2]. Apart from the autoimmune etiology, other ment of confirmed diagnosis (ACTH 1738 pg/
defined by the inability of the adrenal cortex to causes of adrenal insufficiency are: infectious ml [upper normal value 63.3 pg/ml], 8 AM se-
produce sufficient amounts of glucocorticoids adrenalitis (tuberculosis, disseminated fungal rum cortisol 24.01 nmol/L [normal values 275-
and mineralocorticoids [3], [4]. It is a life threat-infections, HIV infection, syphilis), metastatic 555 nmol/L; morning serum cortisol concentra-
ening disorder with variable clinical presenta- cancer (primarily lung, breast, stomach and co- tion less than 80 nmol/L is strongly suggestive
tion, the hormone deficit altering the energy, lon cancer or lymphoma), adrenal hemorrhage of adrenal insufficiency]), the patient received a
salt and fluid homeostasis [2]. or infarction, drugs (ketoconazole, fluconazole, symptomatic treatment with the intent of low-
The delay in making diagnosis or in institut- rifampin, phenytoin, barbiturates, etomidate, ering serum K+ and its effect on cardiac muscle
ing the right treatment explains the life threat- mitotane, etc.) and other rare conditions such as Figure 2. Hyperpigmentation of and to increase serum Na+ and volemia. He re-
ening nature of the disease [5]. adrenoleukodystrophy. the elbows ceived glucose 5% associated with insulin, NaCl
The disease was first described by Thomas 0.9%, gluconic calcium and salbutamol, with no
Addison in 1855. During time, the main etiol- Case report improvements in laboratory findings.
ogy has changed from infectious causes, such A 30-year-old male presented with the follow- Laboratory investigations revealed thrombo- Abdominal ultrasound detected no abnor-
as tuberculosis, to autoimmune causes, asso- ing complaints: asthenia, unintentional weight cytosis (375,000/ul), moderate hyponatremia malities of the adrenal glands that could cause
ciating itself with other autoimmune diseases loss (approximately 9 kilos in the last year), my- (Na 127 mEq/L), severe hyperkalemia (K 7.1

56 57
primary adrenocortical insufficiency (adrenal The best characterized one is polyglandular
hemorrhage/ infarction/ infiltrative process).syn­drome type I, which has its usual onset in
Furthermore, considering the primary adre- childhood and consists of hypothyroidism, ad-
nocortical insufficiency and the hepatocytolysis
renal failure and mucocutaneous candidiasis.
syndrome of unknown etiology, we suspected However, the more common presentation of
an autoimmune mechanism, therefore we dosed: autoimmune adrenocortical insufficiency is as-
antinuclear antibodies (ANA), antimito­chon­ sociated with human leukocyte antigen (HLA)
drial antibodies (AMA), anti-smooth muscle related disorders including type I diabetes mel-
antibodies (SMA), liver-kidney microsome an- litus and autoimmune thyroid disease [2].
tibodies (LKM), all negative; and also thyroid-­ When part of a polyglandular syndrome, the
stimulating hormone (TSH), free thyroxine disease is two times more common in female Figure 4. Addison’s disease emergency bracelets
(FT4), anti-thyroid peroxidase antibodies patients, aged 30 to 50 years old [2].
(ATPO), anti-thyroglobulin antibodies (ATG). The disease becomes symptomatic in a gradu-
Viral markers, anti-HCV antibodies and HBs al manner, beginning with a non-specific clini- the usual gastrointestinal symptoms consist of dehydrogenase type 1 activity before exerting
antigen were negative. Also, HIV infection wascal panel consisting of chronic fatigue, loss of nausea and vomiting, in the acute adrenal cri- biological activity [6].
excluded. The high levels of TSH (10.5 uIU/ appetite, unintentional weight loss, generalized sis, diagnosis can be misled by the suggestion of Patients with associated mineralocorticoid
mL) and ATPO (68.3 U/mL) [normal values weakness, arterial hypotension, musculoskeletal an acute abdomen. Weakness, apathy, confusion deficiency should receive fludrocortisone and
<34 UI/ml], with a normal level of FT4 (0.88 pain, abdominal pain and depression [3]. Apart and fever are also common in the Addisonian should not restrict their salt intake [6].
ng/dl) confirmed the diagnosis of autoimmune from weight loss and orthostatic hypotension due crisis and they can evolve towards shock, coma As described in other studies, the association
thyroiditis with subclinical hypothyroidism. to dehydration, the deficit of gluco- and miner- and finally death in untreated patients [2]. between Addison’s disease and elevated trans-
The patient was referred to the endocrinology
alocorticoids results in hyponatremia, hyperka- The gradual adrenal destruction is suggested aminases is not uncommon [10], [11]. In our
department, with the following diagnosis: Ad- lemia, changes in blood count (normochromic by hyponatremia and hyperkalemia as classi- clinical case, in contrast to the findings of these
dison’s disease, autoimmune thyroiditis, hepa-nor­mo­cytic anemia, eosinophylia, lymphocyto- cal manifestations. Other hematological mani- studies [10], [11], after initiation of steroid re-
tocytolysis syndrome, hypertriglyceridemia andsis) and hypoglycemia [6]. festations include normocytic normochromic placement, transaminase values did not decrease.
acute renal injury. During hospitalization in theHyperpigmentation of the skin and mucous anemia, neutropenia, eosinophilia and relative On the other hand, the associated subclini-
endocrinology department, he received predni- membranes is a classic physical sign and its lymphocytosis. Azotemia with increased con- cal hypothyroidism of this patient can explain
sone, hydrocortisone, bromazepam, omeprazole, presence in association with the above men- centrations of blood urea nitrogen and serum the elevated GPT and triglyceride levels, as
vitamin B1 and B6, NaCl 0.9% and glucose 5%. tioned symptoms should suggest primary adre- creatinine is due to volume depletion and de- thyroid hormones have an important impact
His laboratory findings improved after hy- nocortical insufficiency. This is due to enhanced hydration [2]. on lipid metabolism. They tend to enhance
povolemia correction and the beginning of hor-secretion of ACTH and its stimulant effect on From the moment of diagnosis, primary ad- the utilization of the lipid substrate, increase
monal correction, urea and creatinine normal- melanocytes to produce melanin. Hyperpig- renocortical insufficiency is a lifelong disease, the synthesis and mobilization of triglycer-
ized, and normochromic normocytic anemia mentation is usually generalized, but most fre- which is associated with complications due to ides stored in adipose tissue and increase the
became apparent. The patient’s blood cell count
quently affects the sun exposed areas and pres- its course or to its treatment. concentration of non-esterified fatty acids and
also revealed leukocytosis with neutrophilia sure areas such as knuckles, toes, elbows and Glucocorticoid therapy should be adminis- lipoprotein-lipase activity [12], [13].
secondary to corticoid therapy. knees. It is accompanied by black, dark brown tered to all patients with Addison’s disease. During treatment, patients need to be moni-
The patient was discharged with normal elec-
freckles and hyperpigmentation of the palmar The first choice of treatment should be hy- tored by their primary physician or endocrinolo-
trolyte levels, hypertriglyceridemia, elevated GPT
creases [7]. Vitiligo may also be seen in asso- drocortisone or cortisone acetate divided into gist for any sign of inadequate glucocorticoid re-
(108 UI/L) and normalized renal parameters. ciation with hyperpigmentation due to autoim- two or three oral doses with the highest dose placement (overdosing: weight gain, insomnia
He received as home treatment: fludrocor- mune destruction of melanocytes [8]. in the morning, imitating the circadian pattern and peripheral edema; insufficient dosing: nau-
tisone, prednisone, omeprazole, silymarin and The symptoms of adrenal insufficiency prog- of glucocorticoid secretion. As an alternative to sea, poor appetite, weight loss, lethargy, hyper-
Centrum multivitamins. He was also advised to ress slowly and are usually ignored until some hydrocortisone, especially in patients with re- pigmentation) or inadequate mineralocorticoid
increase his prednisone doses during intercur-stress factors such as infection, trauma, dehydra- duced compliance, prednisolone should be giv- replacement (salt craving, postural hypotension,
rent infections, trauma or surgery. tion can worsen this condition and lead to the en orally, once or twice daily. Hydrocortisone edema) [6], [7].
Addisonian crisis. This consists of penetrating and prednisolone are active glucocorticoids, Glucocorticoids tend to accelerate reduction
Discussion pain in the lower back region, abdomen and whereas cortisone acetate and prednisone re- in bone mass; therefore, in order to detect early
There are two main syndromes in which au- legs, associated with severe vomiting, low blood quire activation via hepatic 11β-hydroxysteroid osteoporosis in patients with overdosed main-
toimmune Addison’s disease frequently occurs. pressure and loss of consciousness [9]. Although

58 59
tenance treatment, a periodic bone dual-energy
X-ray absorptiometry scan can be useful [7], [14].
In the case of polyglandular autoimmune
syndromes that associate hypothyroidism, like
in our patient’s situation, thyroxine replace-
ment can be postponed as thyroid disease may
be steroid responsive [15].
Regarding the education of patients, they
should wear medical alert bracelets (Figure 4.)
so that in case of an emergency situation they
can receive appropriate treatment consisting of
life saving steroids.
They should be given a prescription for par-
enteral hydrocortisone to be used in those situ-
ations when oral intake may not be possible or
in case of marked vomiting or diarrhea [7]. As
a safety measure, patients should always carry
a vial of dexamethasone (or another glucocor-
ticoid) in their handbag. In certain situations,
patients should have a dexamethasone injec-
tion administered intramuscularly, usually in
the thigh, by themselves, a family member or
a friend: after a major injury with substantial
blood loss, or shock; during an episode of nau-
sea and vomiting if oral medications are thrown
up; if there are any signs or symptoms of ad-
renal crisis; if the person wearing the medical
alert bracelet is found unconscious [16].
Patients should be instructed to double or
triple their steroid replacement doses in stress-
ful situations such as infections or surgeries.
Mineralocorticoids need no adjustment in
stressful situations [7].
They should be given a prescription for par-
enteral hydrocortisone to be used in those situ-
ations when oral intake may not be possible or
in case of marked vomiting or diarrhea [7]. As
a safety measure, patients should always carry
a vial of dexamethasone (or another glucocor-
ticoid) in their handbag. In certain situations,
patients should have a dexamethasone injec-
tion administered intramuscularly, usually in
the thigh, by themselves, a family member or
a friend: after a major injury with substantial
blood loss, or shock; during an episode of nau-
sea and vomiting if oral medications are thrown
up; if there are any signs or symptoms of ad-
60 61
renal crisis; if the person wearing the medical ursache für chronisch erhöhte transaminasen, Z
alert bracelet is found unconscious [16]. Gastroenterol, 2006, 44(2):179–183
Patients should be instructed to double or tri- 12. Pucci E, Chiovato L, Pinchera A - Thyroid and
ple their steroid replacement doses in stressful lipid metabolism, Int J Obes, 2000, 24:S109–S112
situations such as infections or surgeries. Mi­ 13. Eshraghian A, Jahromi AH - Non-alcoho-
ne­ra­lo­cor­ti­coids need no adjustment in stressful lic fatty liver disease and thyroid dysfunction: A
situations [7]. systematic review, World J Gastroenterol, 2014,
In conclusion, Addison’s disease remains a 20(25):8102–8109
challenge in regard to its diagnosis, being a 14. Løvås K, Gjesdal CG, Christensen M, Wolff
rare disease with non-specific symptoms, but AB, Almås B, Svartberg J, et al. - Glucocortico-
also in regard to its treatment and life-long id replacement therapy and pharmacogenetics in
surveillance. Addison’s disease: effects on bone, Eur J Endocri-
nol, 2009, 160:993–1002
15. Gharib H, Hodgson SF, Gastineau CF, Scholz
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